bluuebunny/crossref_metadata_2025 huggingface dataset:
The Pharmacokinetics of Toborinone in Subjects with Congestive Heart Failure and Concomitant Renal Impairment and/or Concomitant Hepatic Impairment
Authors: Tammara Brinda , Trang John M. , Kitani Mami , Miyamoto Gohachiro , Bramer Steven L.
Published: April 2003

The pharmacokinetics of toborinone was studied in subjects with congestive heart failure (CHF) and concomitant renal and/or hepatic disease. At the time of admission, subjects were grouped based on estimated creatinine clearance and serum bilirubin. Glomerular filtration rate was assessed using iothalamate clearance. Hepatic function was assessed using the caffeine metabolism test and indocyanine green clearance. No significant differences were observed in mean toborinone pharmacokinetic parameters among the four study groups. Positive correlations were observed between toborinone clearance and the measured indices of renal and hepatic function: creatinine clearance, iothalamate renal clearance, paraxanthine/caffeine ratio, and indocyanine green clearance. Toborinone clearance decreased with decreasing creatinine clearance, decreasing glomerular filtration rate, decreasing demethylation metabolic activity, and decreasing hepatic blood flow, although no significant differences were observed in any mean toborinone pharmacokinetic parameters evaluated among the four study groups.
Famotidine Disposition in Children and Adolescents with Chronic Renal Insufficiency
Authors: Maples Holly D. , James Laura P. , Stowe Cindy D. , Jones Deborah P. , Hak Emily B. , Blumer Jeffrey L. , Vogt Beth , Wilson John T. , Kearns Gregory L. , Wells Thomas G.
Published: April 2003

The pharmacokinetics of intravenous famotidine (0.5 mg/kg, maximum 20 mg) were evaluated in 18 pediatric patients (ages 1–18 years) with stable, chronic renal insufficiency. Subjects were stratified by calculated creatinine clearance (Clcr) into mild (Clcr ≥ 50 to < 90 mL/min/1.73 m2), moderate (Clcr ≥ 25 to < 50 mL/min/1.73 m2), and severe (Clcr ≤ 10 mL/min/1.73 m2) renal insufficiency groups. Significant differences between the mild, moderate, and severe groups were found for elimination rate (Kel), apparent elimination half‐life (t1/2), area under the curve (AUC), and total plasma clearance (Clp) (p < 0.01). Famotidine renal clearance (Clr) was found to be significantly different between the mild and severe groups (p < 0.05). A linear relationship was observed between Clcr and Clp (p < 0.0001; R2 = 0.70). No significant differences in nonrenal clearance (Clnr) were found between groups; however, Clnr as a percentage of Clp was significantly different in the severe group (92.9% ± 7.3% Clnr) compared to the combined mild and moderate groups (21.9% ± 45.6% Clnr) (p < 0.05). It was concluded that the pharmacokinetics of famotidine are significantly altered in children with chronic renal insufficiency; accordingly, dosing should be based on glomerular filtration rate (i.e., Clcr).
Single‐ and Multiple‐Dose Pharmacokinetics of Oral Creatine
Authors: Persky Adam M. , Müller Markus , Derendorf Hartmut , Grant Maria , Brazeau Gayle A. , Hochhaus Günther
Published: April 2003

Supplementation with exogenous creatine (Cr) has shown physiological benefits in humans, but little is known about the pharmacokinetics of Cr in humans. Six healthy males completed an open‐label study consisting of a full pharmacokinetic analysis following a single oral dose of Cr monohydrate (71 mg kg−1) and at steady‐state after 6 days of Cr administration (71 mg kg−1 qid). After the single oral dose, the clearance (CL/F) was 0.20 ± 0.066 L h−1 kg−1, tmax was 1.9 ± 0.88 hours, and Cmax = 102.1 ± 11.2 mg h L−1. At steady‐state, CL/F decreased to 0.12 ± 0.016 L h−1 kg−1, tmax did not change, and Cmax increased to 162.2 ± 30.0 mg L−1. Penetration (AUCMUSCLE/AUCPLASMA) of Cr into the interstitial muscle space, as determined by microdialysis, was 0.47 ± 0.09 and 0.37 ± 0.27 for the single dose and at steady‐state, respectively. Plasma and muscle data were simultaneously fitted with a model incorporating a saturable absorption and first‐order elimination process. In conclusion, repeated dosing of Cr caused a reduction in clearance that could result from saturation of the skeletal muscle pool of Cr.
Pharmacokinetics of Cyclosporine Pre‐ and Post‐Liver Transplantation
Authors: Hebert Mary F. , Wacher Vincent J. , Roberts John P. , Benet Leslie Z.
Published: April 2003

Cyclosporine (CyA) is an immunosuppressant metabolized primarily by the liver and small intestine. The pharmacokinetics (PK) of CyA were studied in 6 patients prior to and 1 to 3 months after liver transplantation (tx). Sixteen blood samples were collected over 24 hours following a 2–3 mg/kg intravenous dose of CyA. PK parameters, presented as mean ± SD, were estimated using noncompartmental techniques. Pre‐tx AUCs (14,540 ± 5200 μg•h/L) were found to be significantly higher than during the post‐tx phase (8120 ± 2870 μg•h/L, p = 0.04). CyA clearance values were lower pre‐tx as compared to post‐tx (0.21 ± 0.06 L/h/kg vs. 0.38 ± 0.14 L/h/kg, respectively). There was no change in volume of distribution. End‐stage liver disease can markedly decrease hepatic clearance of CyA relative to patients with stable hepatic function post—liver tx. The degree of impairment in clearance is not consistent or predictable based on liver function tests.
Pharmacokinetics and Renal Effects of Cidofovir with a Reduced Dose of Probenecid in HIV‐Infected Patients with Cytomegalovirus Retinitis
Authors: Wolf Daniel L. , Rodríguez Carlos A. , Mucci Massimiliano , Ingrosso Antonella , Duncan Barbara A. , Nickens Dana J.
Published: April 2003

To reduce possible nephrotoxicity, intravenous prehydration with normal saline and administration of probenecid must be used with each infusing of the antiviral cidofovir. The recommended standard‐dose probenecid (SDP) regimen is 2 g at 3 hours before cidofovir, then 1 g at 2 and 8 hours after cidofovir (total 4 g). A new regimen of reduced‐dose probenecid (RDP), 2 g at 1 hour before cidofovir without additional probenecid administrations after infusion (total 2 g), was compared with SDP using a randomized, open‐label, parallel design. A single dose of cidofovir (5 mg/kg) was given as a 1‐hour infusion after saline prehydration to 24 HIV‐infected patients (11 males, 13 females) with cytomegalovirus retinitis and good renal function. Blood was sampled for 48 hours and urine for 24 hours after the start of the cidofovir infusion. Cidofovir pharmacokinetics did not differ significantly between groups. Average key pharmacokinetic parameters (Cmax, tmax, Λz, AUC0‐∞, Vss, CL, CLR, fe, ER) for RDP differed by less than 17% from SDP and were consistent with previously reported SDP data. Renal function parameters, other safety endpoints, and adverse events were similar between the groups. Therefore, the reduced‐dose regimen of probenecid provided renal protection after a single dose of cidofovir and did not alter the pharmacokinetics of cidofovir in patients with moderately good renal function. Although the overall pharmacokinetic results do not show a significant difference in cidofovir exposure with the new probenecid regimen, the main issue of safety of the new dose regimen, both relating to renal toxicity and probenecid‐related adverse events, is not adequately addressed in a small study.
The Effect of Food on the Bioavailability of Norethindrone and Ethinyl Estradiol from Norethindrone Acetate/Ethinyl Estradiol Tablets Intended for Continuous Hormone Replacement Therapy
Authors: Boyd Rebecca A. , Zegarac Elizabeth A. , Eldon Michael A.
Published: April 2003

As part of the development of a combination product containing norethindrone acetate and low‐dose ethinyl estradiol for continuous hormone replacement therapy in postmenopausal women, a study was conducted to determine the effect of a high‐fat meal on the bioavailability of norethindrone and ethinyl estradiol from tablets containing 1 mg norethindrone acetate/10 μg ethinyl estradiol. Eighteen healthy postmenopausal women participated in an open‐label, single‐dose, randomized, three‐way crossover study in which 2 × 1/10 norethindrone acetate/ethinyl estradiol tablets were administered fasting and with a high‐fat breakfast, and the same dose was administered in solution. Following each treatment, serial blood samples were collected for 48 hours, and plasma ethinyl estradiol and norethindrone concentrations were determined by a validated gas chromatography/mass spectrometry (GC/MS) method. Individual plasma ethinyl estradiol and norethindrone pharmacokinetic parameters were calculated by noncompartmental methods for each treatment and analyzed by ANOVA to obtain differences between least squares treatment mean values and associated 90% confidence intervals. Rates of ethinyl estradiol and norethindrone availability from tablets administered with food were slower than availability rates from tablets administered while fasting. Systemic exposure to ethinyl estradiol was unaffected by administration of tablets with food, whereas exposure to norethindrone increased by 27%. Because administration of norethindrone acetate/ethinyl estradiol 1/10 tablets with a high‐fat meal did not decrease systemic exposure to norethindrone and ethinyl estradiol, this formulation can be taken without regard to meals.
Safety and Pharmacokinetics of ReN1869: A First Human Dose Study in Healthy Subjects after Single‐Dose Administration
Authors: Skrumsager Birte K. , Ingwersen Steen H. , Gerrits Mireille
Published: April 2003

ReN1869 (NNC 05–1869) is a novel, selective H1 receptor antagonist that has been developed for analgesic purposes. In a first human dose administration study, the safety and pharmacokinetics of seven single oral doses in the range of 3.5 to 95 mg ReN1869 were studied. The study was a randomized, double‐blind, placebo‐controlled, dose‐escalating study in 56 healthy subjects. No serious or severe adverse events were reported. After active doses, an average of 0.6 adverse events (AEs) was reported per subject in comparison to 0.5 AEs per subject after placebo, and the frequency of subjects reporting AEs was not related to dose level. The most frequently reported adverse events were dizziness, fatigue, and somnolence, and their occurrence was not proportional to dose. Vital signs, ECG recordings, and clinical laboratory results showed no changes of clinical relevance. During telemetric monitoring at all dose levels until 4 hours after dosing, no clinically relevant abnormalities were observed. A maximally tolerated dose was not identified. ReN1869 was rapidly absorbed after dosing. The overall mean value of t1/2 and oral clearance was 4.7 hours and 11.7 L/h, respectively. The parameters Cmax and AUC increased proportionally with dose level, whereas all other pharmacokinetic parameters were independent of the dose. In conclusion, single‐dose administration of ReN1869 in doses up to 95 mg exhibited very few adverse events and no clinically relevant effects on any of the observed safety parameters. The pharmacokinetics points to simple first‐order pharmacokinetics for ReN1869. All together, it makes ReN1869 a potential new drug candidate for the treatment of chronic pain and inflammatory conditions of neurogenic origin.
Pharmacokinetics and Pharmacodynamics of a Novel Nizatidine Controlled‐Release Formulation in Healthy Subjects
Authors: Blum Robert A. , Braverman Alan J. , Rice Patricia , Johnson Franklin K.
Published: April 2003

The pharmacokinetics and intragastric pH effects of a novel nizatidine controlled‐release (CR) formulation were compared to a currently marketed immediate‐release (IR) nizatidine formulation (Axid®). The bimodal pulsatile release characteristics of nizatidine CR decreased its Cmax by approximately 42% compared to nizatidine IR while maintaining 90% relative bioavailability; tmax was approximately 1.6 times longer with the CR formulation. These characteristics enabled controlled‐release nizatidine to sustain effective plasma drug concentrations for a greater duration than immediate‐release nizatidine over the dosing intervals. In multiple doses, the 24‐hour AUC ratio for all comparisons of nizatidine CR 150 mg bid, nizatidine CR 300 mg daily, and nizatidine IR 150 mg bid was between 97% and 99%. Mean pH AUC values for nizatidine CR 150 mg bid and nizatidine IR 150 mg bid were similar overall during the 0‐ to 14‐hour and 14‐ to 24‐hour dosing intervals. For the 14‐ to 24‐hour dosing interval, nizatidine CR 150 mg maintained gastric pH over 3.0 and 4.0 for 42% and 27% of the time compared to 39% and 23% for nizatidine IR, respectively. Nizatidine CR 300 mg, compared to the 150‐mg CR and IR regimens, had a greater effect on increasing evening intragastric pH, thus providing support for the potential utility of nizatidine CR 300 mg dosed at night in alleviating nocturnal symptoms of gastroesophageal reflux disease.
Effects of CYP2D6 Genotypes on Plasma Concentrations of Risperidone and Enantiomers of 9‐Hydroxyrisperidone in Japanese Patients with Schizophrenia
Authors: Yasui‐Furukori Norio , Mihara Kazuo , Kondo Tsuyoshi , Kubota Takahiro , Iga Tatsuji , Takarada Yutaka , De Vries Ronald , Kaneko Sunao , Tateishi Tomonori
Published: April 2003

It has been shown that risperidone (+)‐9‐hydroxylation is enantioselectively catalyzed by the polymorphic CYP2D6 in human liver. This study aimed to examine the effect of CYP2D6 genotype on (+)‐9‐hydroxylation of risperidone in schizophrenic patients. Subjects were 38 Japanese schizophrenic inpatients receiving 6 mg/day of risperidone. Plasma concentrations of risperidone and (+)‐ and (−)‐9‐hydroxyrisperidone at steady state were quantified using LC/MS/MS and HPLC with α1 acid‐AGP chiral column, respectively. The CYP2D6*5(*5) and *10 alleles were identified using polymerase chain reaction (PCR) methods. Twenty patients had no mutated allele, 14 had one mutated allele, and 4 had two mutated alleles. There were significant differences in the steady‐state plasma concentrations of risperidone (ANOVA; p < 0.0001) among the three genotype groups, while the CYP2D6 genotype did not affect the steady‐state plasma concentrations of (+)‐9‐hydroxyrisperidone (p = 0.314) or (−)‐9‐hydroxyrisperidone (p = 0.957). The concentration ratio of risperidone to 9‐hydroxyrisperidone was strongly dependent on the CYP2D6 genotypes. This study suggests that CYP2D6 activity strongly influences the steady‐state plasma concentrations of risperidone and risperidone/9‐hydroxyrisperidone concentration ratios but is unlikely to determine enantioselectivity in the steady‐state plasma concentrations of 9‐hydroxyrisperidone in the clinical situation.
Pharmacokinetics of Quinapril in Children: Assessment during Substitution for Chronic Angiotensin‐Converting Enzyme Inhibitor Treatment
Authors: Blumer Jeffrey L. , Daniels Stephen R. , Dreyer William J. , Batisky Donald , Walson Philip D. , Roman Doina , Ouellet Daniele
Published: April 2003

Quinapril pharmacokinetics were studied in infants and children using a novel study design that allowed substitution of quinapril for one dose of the current chronic angiotensin‐converting enzyme (ACE) inhibitor treatment. A total of 24 patients ranging in age from 2.5 to 82 months who were receiving an ACE inhibitor held their usual treatment on the study day and received a 0.2‐mg/kg dose of quinapril syrup. Blood samples were collected through 24 hours postdose, and plasma was analyzed for quinapril and its active metabolite, quinaprilat. Quinapril was rapidly converted to quinaprilat. Quinaprilat concentrations generally peaked 1 to 2 hours postdose and declined with a mean half‐life of 2.30 hours. Dosing on a mg/kg basis resulted in quinaprilat AUC and Cmax values that were generally comparable across the age range of patients in this study. The overall mean AUC0–∞ was 993 ng•h/mL (range: 533–1523), and mean Cmax was 260 ng/mL (range: 70.0–445.5). Quinaprilat CL/F correlated well with body size (body surface area or weight) and creatinine clearance (mL/min). Pharmacokinetic results after a 0.2‐mg/kg dose in infants and children are comparable to those observed following a 10‐mg dose in adults.
Delavirdine Malabsorption in HIV‐Infected Subjects with Spontaneous Gastric Hypoacidity
Authors: Shelton Mark J. , Hewitt Ross G. , Adams John M. , Cox Steve R. , Chambers James H. , Morse Gene D.
Published: April 2003

To determine the impact of gastric hypoacidity and acidic beverages on delavirdine mesylate pharmacokinetics in HIV‐infected subjects, matched subjects with (n = 11) and without (n = 10) gastric hypoacidity received delavirdine 400 mg tid with either water or an acidic beverage (usually orange juice). The pharmacokinetics of delavirdine and its N‐desalkyl metabolite were determined over 8 hours after 14 days of each treatment. Gastric pH was measured at baseline and during each pharmacokinetic evaluation. Delavirdine exposure (Cmax, AUC0→8h, and Cmin) was ∼ 50% lower and the extent of delavirdine metabolism was higher in subjects with gastric hypoacidity. Orange juice produced a lower mean gastric pH compared to water and increased delavirdine absorption by 50% to 70% in subjects with gastric hypoacidity. However, orange juice had a marginal impact on delavirdine exposure in subjects without gastric hypoacidity. HIV‐infected subjects with gastric hypoacidity significantly malabsorb delavirdine. Delavirdine administration with acidic beverages improves, but does not normalize, absorption in these subjects.
Effect of Rofecoxib on Prednisolone and Prednisone Pharmacokinetics in Healthy Subjects
Authors: Schwartz Jules I. , Mukhopadhyay Saurabh , Porras Arturo G. , Viswanathan‐Aiyer Kala‐Jyoti , Adcock Sherilyn , Ebel David L. , Gertz Barry J.
Published: April 2003

Patients receiving nonsteroidal anti‐inflammatory drug therapy may also require administration of corticosteroids, particularly patients with rheumatoid arthritis. To investigate the effect of rofecoxib on the single‐dose pharmacokinetics of oral prednisone and intravenous prednisolone, the authors conducted a randomized, double‐blind, placebo‐controlled crossover study in 12 healthy subjects. Oral rofecoxib (250.0 mg/day for 14 days) failed to influence prednisone or prednisolone pharmacokinetics after intravenous prednisolone or oral prednisone administration. The geometric mean ratio (GMR) (90% confidence interval) of prednisolone AUC∞ (rofecoxib/placebo) following intravenous and oral corticosteroid was 0.97 (0.94, 1.01) and 0.99 (0.91, 1.08), respectively. Similarly, the prednisone AUC∞ GMRs (rofecoxib/placebo) after intravenous and oral corticosteroid were 1.03 (0.95, 1.11) and 1.08 (0.92, 1.28), respectively. The absence of an effect of rofecoxib on the pharmacokinetics of oral prednisone or intravenous prednisolone indicates that no adjustment in dose of this corticosteroid is necessary when administered concurrently with rofecoxib.
Effect of Inhaled Steroids on Bone Mineral Density: A Meta‐Analysis
Authors: Sharma Pramod Kumar , Malhotra Samir , Pandhi Promila , Kumar Narinder
Published: April 2003

Inhaled corticosteroids are currently considered first‐line agents for the treatment of asthma. Medium‐ to long‐term administration of inhaled steroids may be associated with bone loss. Various studies have evaluated their effect on bone mineral density (BMD); some have shown loss of BMD with steroid treatment, but others have failed to do so. The present meta‐analysis was undertaken to determine the possible effect of inhaled steroids on bone density. Literature was collected using computerized (MEDLINE) and manual searches using index medicus and checking cross‐references of the published articles. The studies identified were screened for inclusion/exclusion criteria. Grouped means (XT/XC) and pooled standard deviations (SDT/SDC) for the treatment group (XT [95% CI] = 1.144 [1.019–1.269]; SDT = 0.163, g/cm2) and control group (XC [95% CI] = 1.193 [1.073–1.313]; SDC = 0.157, g/cm2) were worked out respectively for the selected studies. Finally, a comparison between grouped means of steroid‐treated and control groups was done by two‐sample t‐test at the 5% level of significance. The results of the meta‐analysis showed that although the mean BMD of the steroid‐treated group was reduced by 4.1% as compared to the control group, this failed to achieve statistical significance (p = 0.8; 95% CI for the mean difference between two groups = 0.028 − 0.070 g/cm2). It is concluded that inhaled steroids for the treatment of asthma can be considered safe with respect to their effect on bone loss.
Effect of High‐Fat Breakfast and Moderate‐Fat Evening Meal on the Pharmacokinetics of Vardenafil, an Oral Phosphodiesterase‐5 Inhibitor for the Treatment of Erectile Dysfunction
Authors: Rajagopalan Prabhu , Mazzu Arthur , Xia Chenghua , Dawkins Ray , Sundaresan Pavur
Published: April 2003

The effects of food on the pharmacokinetics of vardenafil were examined in 25 healthy adult males. Single‐dose vardenafil 20 mg was administered in a randomized four‐way crossover design after an overnight fast (at 8 a.m.), after consumption of a high‐fat breakfast (at 8 a.m.), on an empty stomach (at 6 p.m.), and after a typical moderate‐fat evening meal (at 6 p.m.). Serial blood samples were analyzed for vardenafil and metabolite (M1) levels. When administered after an overnight fast and after a high‐fat breakfast, vardenafil geometric mean Cmax was 17.14 and 14.0 μg/L, respectively, and AUC was 66.78 and 67.09 μg•h/L, respectively; the median tmax was 1 hour under fasting conditions and 2 hours with consumption of high‐fat breakfast. When administered in the evening on an empty stomach and after a moderate‐fat meal, vardenafil geometric mean Cmax was 14.22 and 13.04 μg/L, respectively, and AUC was 51.97 and 59.12 μg•h/L, respectively. The median tmax was 1 hour after fasting or a moderate‐fat meal in the evening. All treatments were well tolerated. Thus, while a high‐fat meal may alter Cmax slightly and delay the absorption up to 1 hour, a moderate‐fat meal has no clinically relevant effect on vardenafil pharmacokinetics. Dosage changes are not warranted based on the wide therapeutic index and the efficacy observed with vardenafil in Phase III studies that were not restricted with respect to food.
Topical Hemostatic Effect of a Common Ornamental Plant, the Geraniaceae Pelargonium zonale
Authors: Páez Ximena , Hernández Luis
Published: April 2003

Geranium has been traditionally used as a local hemostatic medicine in some Andean regions, but this effect has not been tested in controlled experiments. In the present report, the leaves of a geraniaceae (Pelargonium zonale) were tested on a bleeding rat model. The bleeding time was 50% shorter in the geranium leaf juice treatment group (18.10 ± 2.03 min) and 80% shorter in the geranium crushed‐leaf group (7.10 ± 0.88 min) than in the control (nontreatment) group (37.6 ± 3.04 min), p < 0.0001. Bleeding time with guava (Psidium guajava) crushed leaves (39.90 ± 1.54 min) was not different from the control group. A proved hemostatic agent, gelatin sponge, had a similar effect as geranium juice (16.7 ± 3.32 min) in the same animal model. A buffer solution at pH 3 (the same pH as the geranium leaf extract) did not have any hemostatic effect, and the bleeding time (39.3 ± 2.71 min) was not different from the control group. The dilution 1:4 geranium leaf juice at pH 3 (25.6 ± 3.08 min) or pH 5 (28.8 ± 3.98 min) still had a statistically significant hemostatic effect. The results confirm the hemostatic effect of P. zonale leaves and show that it is similar (geranium leaf juice) or better (crushed geranium leaves) than the hemostatic effect of a commercial hemostatic sponge. It seems that the hemostasis caused by P. zonale extract leaves is not due to its low pH. The potential benefits as a new, inexpensive, safe, and easily available natural topical hemostatic agent are discussed.
Single‐ and Multiple‐Dose Pharmacokinetics of Etoricoxib, a Selective Inhibitor of Cyclooxygenase‐2, in Man
Authors: Agrawal Nancy G. B. , Porras Arturo G. , Matthews Catherine Z. , Rose Mark J. , Woolf Eric J. , Musser Bret J. , Dynder Andrea L. , Mazina Katherine E. , Lasseter Kenneth C. , Hunt Thomas L. , Schwartz Jules I. , McCrea Jacqueline B. , Gottesdiener Keith M.
Published: April 2003

The single‐ and multiple‐dose pharmacokinetics of etoricoxib, a selective inhibitor of cyclooxygenase‐2, were examined in two clinical studies. Single‐dose pharmacokinetics—including dose proportionality, absolute bioavailability of the highest dose‐strength (120‐mg) tablet, and the effect of a high‐fat meal on the bioavailability of that tablet—were investigated in a two‐part, open, balanced crossover study in two panels of healthy subjects (12 per panel). Steady‐state pharmacokinetics were investigated in an open‐label study in which 24 healthy subjects were administered 120‐mg single and multiple (once daily for 10 days) oral doses of etoricoxib tablets. The pharmacokinetics of etoricoxib were found to be consistent with linearity through doses at least twofold greater than the highest anticipated clinical dose of 120 mg. Etoricoxib administered as a tablet was rapidly and completely absorbed and available; the absolute bioavailability was estimated to be 100%. A high‐fat meal decreased the rate of absorption without affecting the extent of absorption of etoricoxib; therefore, etoricoxib can be dosed irrespective of food. Steady‐state pharmacokinetics of etoricoxib, achieved following 7 days of once‐daily dosing, were found to be reasonably predicted from single doses. The accumulation ratio averaged 2.1, and the corresponding accumulation t1/2 averaged 22 hours, supporting once‐daily dosing. Etoricoxib was generally well tolerated.
Pharmacokinetics and Pharmacodynamics of a Single Bolus of Propofol 2% in Healthy Volunteers
Authors: Abad‐Santos Francisco , Gálvez‐Múgica Ma Angeles , Santos Ma Angeles , Novalbos Jesús , Gallego‐Sandín Sonia , Méndez Paloma , Casimiro Cesar , Gilsanz Fernando
Published: April 2003

This study was undertaken to assess the bioequivalence between a new formulation of propofol 2% and the commercially available product Diprivan. Secondary objectives were to compare the times to onset of and emergence from hypnosis, the hemodynamic effects, and the safety profiles. Twelve healthy male volunteers were included in a randomized crossover study. Subjects were administered a 2‐mg/kg single bolus injection of each formulation separated by a 7‐ to 10‐day washout period. Plasma propofol was determined by reversed‐phase liquid chromatography with fluorescence detection. Eleven subjects completed the study, and both formulations were considered bioequivalent. There were no serious or severe adverse events. The concentration‐time profiles of all the subjects could adequately be described using a three‐compartment model. The mean times to cessation of counting out loud (17 vs. 18 s) and to eye opening (245 vs. 244 s) were not statistically different between treatment groups. Moreover, they seem to show some degree of pharmacodynamic bioequivalence, although a higher number of subjects are necessary to unequivocally demonstrate it.
Population Kinetics, Efficacy, and Safety of Dichloroacetate for Lactic Acidosis Due to Severe Malaria in Children
Authors: Agbenyega Tsiri , Planche Tim , Bedu‐Addo George , Ansong Daniel , Owusu‐Ofori Alex , Bhattaram Venkatesh A. , Nagaraja Nelamangala V. , Shroads Albert L. , Henderson George N. , Hutson Alan D. , Derendorf Hartmut , Krishna Sanjeev , Stacpoole Peter W.
Published: April 2003

The authors conducted a randomized, double‐blind, placebo‐controlled trial of intravenous dichloroacetate (DCA) for the purpose of treating lactic acidosis in 124 West African children with severe Plasmodium falciparum malaria. Lactic acidosis independently predicts mortality in severe malaria, and DCA stimulates the oxidative removal of lactate in vivo. A single infusion of 50 mg/kg DCA was well tolerated. When administered at the same time as a dose of intravenous quinine, DCA significantly increased the initial rate and magnitude of fall in blood lactate levels and did not interfere with the plasma kinetics of quinine. The authors developed a novel population pharmacokinetic‐pharmacodynamic indirect‐response model for DCA that incorporated characteristics associated with disease reversal. The model describes the complex relationships among antimalarial treatment procedures, plasma DCA concentrations, and the drug's lactate‐lowering effect. DCA significantly reduces the concentration of blood lactate, an independent predictor of mortality in malaria. Its prospective evaluation in affecting mortality in this disorder appears warranted.
Pharmacogenetics and Pharmacogenomics in Drug Development and Regulatory Decision Making: Report of the First FDA‐PWG‐PhRMA‐DruSafe Workshop
Authors: Lesko Lawrence J. , Salerno Ronald A. , Spear Brian B. , Anderson Donald C. , Anderson Timothy , Brazell Celia , Collins Jerry , Dorner Andrew , Essayan David , Gomez‐Mancilla Baltazar , Hackett Joseph , Huang Shiew‐Mei , Ide Susan , Killinger Joanne , Leighton John , Mansfield Elizabeth , Meyer Robert , Ryan Stephen G. , Schmith Virginia , Shaw Peter , Sistare Frank , Watson Mark , Worobec Alexandra
Published: April 2003

The use of pharmacogenetics and pharmacogenomics in the drug development process, and in the assessment of such data submitted to regulatory agencies by industry, has generated significant enthusiasm as well as important reservations within the scientific and medical communities. This situation has arisen because of the increasing number of exploratory and confirmatory investigations into variations in RNA expression patterns and DNA sequences being conducted in the preclinical and clinical phases of drug development, and the uncertainty surrounding the acceptance of these data by regulatory agencies. This report summarizes the outcome of a workshop cosponsored by the Food and Drug Administration (FDA), the Pharmacogenetics Working Group (PWG), the Pharmaceutical Research and Manufacturers of America (PhRMA), and the PhRMA Preclinical Safety Committee (DruSafe). The specific aim of the workshop was to identify key issues associated with the application of pharmacogenetics and pharmacogenomics, including the feasibility of a regulatory “safe harbor” for exploratory genome‐based data, and to provide a forum for industry‐regulatory agency dialogue on these important issues.
Self-Congruency as a Cue in Different Advertising-Processing Contexts
Authors: Chang Chingching
Published: April 2003

This study examines how self-congruent advertising messages affect ad and brand evaluations in different contexts. Within the Elaboration Likelihood Model, this study proposes that an ad message's congruency with subjects' self-concepts serves as a peripheral cue when subjects do not have the motivation to process information. Experiment 1 shows that subjects rely on messages' self-congruency in forming brand and ad attitudes in positive affective states, in which motivation to engage in message elaboration is low, whereas subjects in negative affective states do not. Moreover, in line with past evidence that the lack of motivation to process induced by positive affective states can be overridden by factors enhancing individuals' motivation, Experiment 2 demonstrates that when a product is high involving, as opposed to low involving, attitudes toward the product are less likely to be developed based on the messages' self-congruency, even when subjects' affective states encourage a peripheral mode of processing.
Effects of News Coverage on Policy Attention and Actions
Authors: Yanovitzky Itzhak
Published: April 2003

Studies that examine the media-policy connection often neglect to fully explore the dynamic nature of this association over time. It is suggested that a conceptual framework that separates media effects on policy makers' attention to issues from effects on their actual behavior (or policy actions) may be key for studying the dynamic relationship between information in the media and policy response to this information. Employing this approach to the case of drunk driving between 1978 and 1995, it was found that heightened media attention to the drunk-driving problem at the beginning of the issue-attention cycle (the early 1980s) attracted greater policy attention to this issue and pressured policy makers to generate immediate, short-term solutions to the problem. Yet, once the volume of media attention to this issue started to wane (from the late 1980s onward), policy preferences gradually shifted to long-term solutions.
Agenda Setting and Issue Salience Online
Authors: Roberts Marilyn , Wanta Wayne , Dzwo Tzong-Horng (Dustin)
Published: April 2003

This study examined the agenda-setting process and the role it may play on the Internet, specifically in electronic bulletin boards (EBB). Online media coverage of four issues from five news media were downloaded during the 1996 fall political campaign. The frequency of EBB discussions of each issue served as the surrogate for the public agenda. An ARIMA model cross-correlational test showed EBB discussions of three issues—immigration, health care, and taxes—correlated with news media coverage, with time lags varying from 1 day to 7 days. Only for abortion did the media have no apparent agenda-setting effect. Media coverage apparently can provide individuals with information they can use in their EBB specific-issue discussions.
A Multilevel Approach to Civic Participation
Authors: Kang Naewon , Kwak Nojin
Published: April 2003

This study employed Sampson’s multilevel system model to investigate how individual-and neighborhood-level residential characteristics are related to individuals’ civic participation. Furthermore, this study examined whether the effects of communication variables on civic participation vary depending on these residence-related factors. The findings show the significant impacts of residential variables, individual length of residence and neighborhood residential stability, and they support prior research that has evidenced the significance of communication behaviors—interpersonal network, public affairs newspaper and television use, and time spent watching television. Notably, this study revealed significant interactive relationships between residential variables and media use in generating civically oriented citizens: The use of local public affairs news on TV is more likely to lead to community participation among those living in a neighborhood with lower residential mobility, and time spent watching TV tends to be negatively related to civic engagement among those whose residence in a community is shorter.
Explaining Cultural Differences in Evaluations of Emotional Support Behaviors
Authors: Burleson Brant R. , Mortenson Steven R.
Published: April 2003

Research suggests that affirming, emotion-focused expressions of comfort effectively provide social support. However, little research has examined whether preferred approaches to providing support differ as a function of culture and, if so, why. This study sought to document, for both the Barbee and Cunningham typology of support behaviors and the Burleson hierarchy of comforting messages, whether there are cultural differences in preferred approaches to emotional support provision and, if so, what factors might account for these differences. Participants completed assessments of (a) the appropriateness of using solace, solve, dismiss, and escape behaviors, (b) the perceived sensitivity of comforting messages varying in degree of person centeredness, (c) interaction goal orientation, (d) the value placed on skill in comforting, and (e) collectivist and individualist values. Analyses indicated there were significant cultural differences in evaluations of support behaviors and that these differences were partially mediated by interaction goals and value orientations.
Enhancing Mutual Understanding in Synchronous Computer-Mediated Communication by Training
Authors: Cornelius Caroline , Boos Margarete
Published: April 2003

Ineffective use of text-based synchronous computer-mediated communication (CMC), that is, chats, may affect the quality of communicative exchange compared to effective use and to face-to-face (FtF) communication. Especially in groups making decisions in equivocal judgmental tasks, inappropriate use of the CMC medium often impairs performance. Users need high communication and media competencies to overcome the negative effects brought about by the technology. Without intervention, mutual understanding and satisfaction with the group process are reduced in computer-mediated decision groups. Training that helps participants adapt to the medium should provide them with the needed competencies. The authors found a complex pattern of process and outcome effects with the best performance scores in the FtF condition, performance scores in CMC with training approximating those of the FtF condition, and lowest performance scores in CMC without training.
Exploring the Framing Effects of Emotion
Authors: Nabi Robin L.
Published: April 2003

The persuasive effects of emotions have been the focus of burgeoning interest in recent years. Rather than considering how emotions function within traditional paradigms of attitude change, this research explores the possibility that emotions serve as frames for issues, privileging certain information in terms of accessibility and thus guiding subsequent decision making. This study’s results offer evidence that fear and anger can differentially affect information accessibility, desired information seeking, and policy preference, though these effects may be contingent on schema development. These findings support not only the relationship between emotions and frames but also the importance of the discrete emotion perspective in persuasive contexts.
Dimensions Associated with Assessments of Sex Offender Recidivism Risk
Authors: Roberts Caton F. , Doren Dennis M. , Thornton David
Published: April 2003

This research explored empirical dimensions of sex offender recidivism risk. Study 1 portrayed descriptive statistics and factor structure information concerning actuarial risk instruments and diagnoses derived from a sample of sex offenders being evaluated for civil commitment in Wisconsin. Study 2 used a sample from England and Wales to analyze the relationships between individual risk factors commonly found as items within actuarial scales. Factor structure results from Study 2 conceptually overlapped those found in the first sample, and variables developed from this factor structure predicted sexual reconviction as well. Results from these two studies are discussed in terms of separable components of risk for sexual recidivism and the roles those components may play in processes underlying sexual reoffense.
Motivation as a Predictor of Therapeutic Engagement in Mandated Residential Substance Abuse Treatment
Authors: Hiller Matthew L. , Knight Kevin , Leukefeld Carl , Simpson D. Dwayne
Published: April 2003

Studies of community-based substance abuse treatment indicate that motivation for treatment is critical for retaining clients in the program and for their becoming therapeutically engaged in the recovery process. Relatively little work, however, has examined the effect of motivation on therapeutic engagement in criminal justice settings. Baseline and during-treatment data were collected prospectively from 419 probationers remanded to a 6-month modified therapeutic community. Findings showed that desire for help and treatment readiness were associated with indicators of therapeutic engagement even after statistically controlling for additional factors that could have confounded these relationships. Targeted readiness and induction interventions are therefore recommended for offenders with low motivation who are remanded to treatment in correctional settings.
Perceived Coercion and Treatment Need Among Mentally Ill Parolees
Authors: Farabee David , Shen Haikang , Sanchez Sylvia
Published: April 2003

Much of the early literature concerning coerced treatment relied on measures such as legal pressure. The past 5 years saw a further development in the measurement of coercion based on patients’ perceptions. In both cases, however, coercion levels are based on external elements of coercion without taking into account the prospective patients’ perceived need for treatment. To better understand the relationship between these constructs, the authors conducted interviews with mentally ill parolees mandated into outpatient treatment ( N = 97). Patients were asked to respond to the five-item MacArthur Perceived Coercion Scale (PCS) and several other items designed to reflect perceived treatment need. A cluster analysis of these items resulted in the five PCS items and the two perceived treatment need (PTN) items emerging as separate clusters. Moreover, the majority of the patients who reported no control over admission to the clinic recognized their need for psychiatric treatment.
Coercion and Sex Offenders
Authors: Burdon William M. , Gallagher Catherine A.
Published: April 2003

Sex offenders represent a variable group of law violators, yet they are often viewed as suffering from a generalized mental illness and in need of treatment and management different from other types of criminal offenders. This often occurs within the context of some form of coercion. However, little is known about how coercion adds to or detracts from the successful treatment and control of sex offenders. This article explores the historical role of coercion in treating sex offenders and controlling their behavior along with the changing and evolving emphasis on treatment of sex offenders. It concludes with a discussion of the proper role that coercion can and should play relative to the overall effectiveness of treatment and a theoretical explanation of how coerced sex offenders may ultimately benefit from treatment.
The Influence of Professional Orientation on Detention Officers' Attitudes Toward The Use of Force
Authors: Griffin Marie L.
Published: April 2003

With few exceptions, little attention has been paid to detention officers and their attitudes toward use of force against inmates. A number of studies have focused attention on the punitive, custodial, and rehabilitative attitudes that form an officer's professional orientation and the way in which such attitudes influence the nature of officer/inmate interaction. However, the relationship between professional orientation and attitudes toward use of force remains unexplored. Based on a survey of 617 detention officers working in seven jails, this article uses multivariate analyses to examine the independent effects of individual characteristics, work environment factors, and professional orientation on officers' reported readiness to use force in a county jail. The results indicate that a detention officer's readiness to use force is influenced by some, but not all, types of professional attitudes toward inmates and interactions with inmates.
Police Handling of the Mentally Ill in Domestic Violence Situations
Authors: Finn Mary A. , Stalans Loretta J.
Published: April 2003

This article provides a systematic test of the reasoning underlying officers' decisions to civilly commit or arrest hallucinating suspects of domestic violence. Police officers ( N = 257) read hypothetical scripts that manipulated three conditions (the suspect's mental state, antagonism or cooperativeness between disputants, and presence or absence of victim injury) and responded to questions about their inferences and responses. Findings indicate that mentally ill husbands were not more likely to be arrested, but officers who blamed the victim or held stereotypic views supportive of the use of violence were less likely to arrest. Police officers who believed that mental hospitals typically accepted violent persons, perceived that severe harm to the victim was likely if the suspect remained in the home, and regarded the suspect as cooperative with them were more likely to seek civil commitment.
Offender Risk Assessment
Authors: Bonta James
Published: April 2003

During the past 20 years, there have been significant developments in the area of offender assessment. As a result, this knowledge has placed the field in a position to construct guidelines as to what should characterize useful and effective offender assessment instruments. The author’s suggestions as to what constitutes good assessment ranges from the noncontroversial (e.g., actuarial instruments) to the more contentious (e.g., lessening one’s reliance on static risk scales). Whether the reader agrees with the views expressed, it is hoped that the force of the empirical arguments will at least provoke some careful consideration rather than summarily dismissing them.
Offender Treatment Attrition and its Relationship with Risk, Responsivity, and Recidivism
Authors: Wormith J. Stephen , Olver Mark E.
Published: April 2003

This investigation examined factors contributing to attrition from correctional treatment and the implication that treatment noncompletion may have for issues concerning risk, recidivism, and responsivity. Participants included 93 violent offenders who had been referred to an intensive treatment program in a maximum security correctional facility. Descriptive information, program participation, and recidivism data were gathered from comprehensive institutional and police records. Treatment noncompleters had less formal education and less employment history in the community. They were more likely to be of aboriginal ancestry and classified to maximum security, scored more poorly on several treatment process variables, and were higher risk offenders. Subsequent analyses demonstrated that very high-risk aboriginal offenders were particularly vulnerable to dropping out of treatment (80%). The findings are discussed with respect to the principles of risk and responsivity.
Putting the “What Works” Research into Practice
Authors: Ferguson Jennifer L.
Published: April 2003

Significant advances have been made in correctional research over the past decade. The research has highlighted the key elements of effective correctional assessment and treatment. However, organizations that wish to engage in effective correctional services by implementing the findings of correctional research have been given minimal practical guidance. This article discusses the experience of one probation department and its implementation of a risk and needs assessment tool as part of the daily practice of the organization. The implementation steps are identified as well as the challenges faced and the lessons learned.
Juvenile Correctional Officers’ Perceived Fear And Risk Of Victimization
Authors: Gordon Jill A. , Moriarty Laura J. , Grant Patricia H.
Published: April 2003

In this exploratory study, the authors examined perceived fear and risk of victimization among juvenile correctional officers at two juvenile detention centers in Virginia. Expanding on previous work, four scales were created to measure fear of victimization and risk of victimization at individual and collective levels. Our analyses revealed no difference in fear or risk of victimization levels among the juvenile correctional officers based on the type of correctional facility; however, gender was found to be statistically significant in all models. Female officers were more likely to have a higher level of perceived fear and risk of victimization at the individual and collective levels than were male officers. Race and education were also found to be significant factors in one model, perceived risk of victimization at the individual level.