bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of a non‐linear IVIVC model for a diltiazem extended release formulation
Authors: Sirisuth Nattee , Augsburger Larry L. , Eddington Natalie D. 
Published: January 2005

AbstractTo develop and validate internally an in vitro–in vivo correlation (IVIVC) for a diltiazem multi‐particulate bead extended release formulation. In vitro dissolution of diltiazem capsules was examined using the following methods: USP Apparatus II (paddle) at 100 rpm and USP Apparatus III at 30 dpm. Seven healthy subjects received three diltiazem formulations (90 mg): slow (S), moderate (M), fast (F) releasing and an oral solution (90 mg). Serial blood samples were collected over 48 h and analyzed by a validated HPLC assay using ultraviolet detection. The f2 metric (similarity factor) was used to analyze the dissolution data. Linear and non‐linear (quadratic, cubic, and sigmoid functions) correlation models were developed using pooled fraction dissolved (FRD) and fraction absorbed (FRA) data from various combinations of the formulations. Predicted diltiazem concentrations were obtained by convolution of the in vivo dissolution rates. Prediction errors were estimated for Cmax and AUC to determine the validity of the correlation.Apparatus II using purified water was found to be the most discriminating dissolution method. Significant intersubject (CV%>50) was observed for Cmax and AUC. The quadratic M/F IVIVC model provided a significant relationship between FRD and FRA when using either two or three of the formulations. An average percent prediction error for Cmax and AUC for all formulations was 12.4% and 9.2%, respectively.The prediction errors observed for Cmax and AUC suggest that the predictability of the quadratic IVIVC model is inconclusive, as such, external validation studies are required. Copyright © 2002 John Wiley & Sons, Ltd.
Pharmacokinetics of controlled‐release verapamil in healthy volunteers and patients with hypertension or angina
Authors: Gupta Suneel , Modi Nishit B. , Sathyan Gayatri , Ho Pai‐ling , Aarons Leon 
Published: January 2005

AbstractAims: To study the dose‐ranging population pharmacokinetics of controlled release verapamil in healthy subjects and patients with angina or hypertension. To characterize the pharmacodynamics of controlled‐release verapamil in patients with hypertension.Methods: Dose‐ranging studies were conducted in healthy volunteers and patients with hypertension and angina. Subjects received doses of 120, 180, 360, or 540 mg racemic verapamil as an osmotic controlled‐release formulation. A population pharmacokinetic model involving zero‐order release of verapamil into the gastrointestinal tract with first‐order absorption and elimination was used to describe the steady‐state plasma concentration profile for R‐ and S‐verapamil. A population sigmoid Emax pharmacodynamic model was used to describe the effect of R‐ and S‐verapamil on mean arterial blood pressure.Results: S‐verapamil had an approximate 4‐fold greater apparent clearance than R‐verapamil in both healthy volunteers and patients. The apparent plasma clearance of R‐ and S‐verapamil in healthy volunteers decreased over the dose range of 120–540 mg. A similar dose‐dependent decrease in apparent plasma clearance was also noted in patients. None of the patient demographic variables examined (age, total body weight, lean body weight, body mass index, and height) explained the variability in verapamil pharmacokinetics. The pharmacodynamic model describing the relationship between verapamil plasma concentration and mean arterial blood pressure indicated that the S‐verapamil had a 3.6‐fold lower estimated EC50 compared to R‐verapamil.Conclusions: The results from this dose‐ranging pharmacokinetic investigation in healthy volunteers and patients are consistent with previous reports in healthy subjects. S‐verapamil is cleared more rapidly than R‐verapamil and the estimated EC50 for S‐verapamil was 3.6‐fold lower than for R‐verapamil. Estimated EC50 values for R‐ and S‐verapamil decreased with increasing age and decreasing weight. Copyright © 2002 John Wiley & Sons, Ltd.
Influence of fluconazole on the pharmacokinetics of omeprazole in healthy volunteers
Authors: Kang Byoung C. , Yang Chang Q. , Cho Hae K. , Suh Ok K. , Shin Wan G. 
Published: January 2005

AbstractInfluence of fluconazole on the pharmacokinetics of omeprazole was evaluated by single oral administration of omeprazole capsule 20 mg (control group), or single oral administration of fluconazole capsule, 100 mg, and omeprazole, 20 mg, after 4 days of daily oral administration of fluconazole, 100 mg (treated group), to 18 healthy male volunteers. Omeprazole is extensively metabolized in the liver through 5‐hydroxylation and sulfoxidation reactions catalyzed predominantly by CYP2C19 and CYP3A4, respectively. Fluconazole is a potent competitive inhibitor of CYP2C19 and a weak inhibitor of CYP3A4. In treated group, the area under the plasma concentration–time curve of omeprazole from time zero to time infinity (AUC) was significantly greater (3090 vs 491 ng h/ml), terminal half‐life of omeprazole was significantly longer (2.59 vs 0.85 h), and peak plasma concentration of omeprazole (Cmax) was significantly higher (746 vs 311 ng/ml) than that in control group. The greater AUC and higher Cmax in treated group could be due to inhibition of omeprazole metabolism by fluconazole. Copyright © 2002 John Wiley & Sons, Ltd.
A study of streptomycin blood level information of patients undergoing hemodialysis
Authors: Akaho Eiichi , Maekawa Takashi , Uchinashi Masako , Kanamori Ryuichi 
Published: January 2005

AbstractPharmacokinetic feature of streptomycin (SM) was investigated before and during hemodialysis (HD) in four patients with renal failure undergoing HD. SM concentrations were assayed by using TDX SM KIT (DAINABOT). Patients received 10 mg/kg of SM by intramuscular injection before HD.Pharmacokinetic parameters of SM intramuscular injection before HD were ka=2.38±0.53 h−1; ke=0.0130±0.0025 h−1; Vd=0.313±0.026l/kg and t1/2=55.6±10.4 h.The maximum concentration (Cmax) of SM was observed at about 2 h after the SM administration and the mean serum concentration of SM was 30.4 µg/ml; even 4 h after the SM injection, the concentration still remained in a range over 30 µg/ml. The data suggest that a possible toxicity might have appeared in the patients.During the hemodialysis an average t1/2 value was 3.32 h. This value is close to the value of a healthy person. The ke value of patient A during the hemodialysis became 24 times as large as that observed before the hemodialysis. On the average it was 17 times as large as that observed before the hemodialysis. Thus, it was found that the values of pharmacokinetics parameters such as ke and t1/2 during the hemodialysis were similar to those of a healthy person, although there are some variations. Copyright © 2002 John Wiley & Sons, Ltd.
Pharmacokinetics and dose proportionality of BMS‐204352 after intravenous administration to dogs
Authors: Krishna Rajesh , Shah Vinod R. , Mantha Subbaro , Vachharajani Nimish N. , Srinivas Nuggehally 
Published: January 2005

AbstractBMS‐204352 is a novel maxi‐K channel opener that is being developed for the treatment for stroke. The current study was designed to evaluate the dose proportionality and pharmacokinetics of BMS‐204352 in dogs. In an open, three‐way crossover study, three beagle dogs received a single intravenous dose of BMS‐204352 as a 6‐min infusion into the femoral vein at 0.4, 0.9, and 2.0 mg/kg dose levels. There was at least a 1‐week washout period between treatments. Serial blood samples were collected for up to 32 h post dose and plasma samples were analyzed for the concentrations of intact BMS‐204352 using a validated liquid chromatographic mass spectrometric (LC/MS) method. Pharmacokinetic analysis was performed using a non‐compartmental method. Results indicated that peak BMS‐204352 concentrations (Cmax) and area under the plasma concentration–time curves (AUC) values increased in a dose proportional manner. Mean residence time (MRT, 18.2–21.9 h) and elimination half‐life (Thalf, 13.5–17 h) did not change with dose. There was no dose dependency in the mean BMS‐204352 total body clearance (CLT, 134–158 ml/h/kg) and mean steady state volume of distribution (VSS, 2839‐3291 ml/kg). The high VSS value indicated that BMS‐204352 was distributed extensively in the extravascular tissues. In conclusion, BMS‐204352 exhibits linear pharmacokinetics over the dose range tested (0.4–2 mg/kg). Copyright © 2002 John Wiley & Sons, Ltd.
Minimal effect of ketoconazole on cyclosporine (SangCyATM) oral absorption and first‐pass metabolism in rats: evidence of a significant vehicle effect on SangCyA absorption
Authors: Wong Susan , Wong Harrison T. , Wacher Vincent J. 
Published: January 2005

AbstractThe current work evaluated the effect of the CYP3A inhibitor ketoconazole on the oral absorption and first‐pass metabolism of cyclosporine administered as the SangCyA formulation. Groups of 6 male Sprague–Dawley rats were administered SangCyA (5 and 15 mg/kg) by oral gavage alone and with ketoconazole (30 mg/kg). Blood cyclosporine levels were measured over 6 h, encompassing the cyclosporine absorption window. A significant vehicle effect on SangCyA absorption was observed. Comparing a 15 mg/kg dose, cyclosporine Cmax (mean±SD 1.12±0.16 µg/ml) and AUC0−6 (5.34±0.71 µg h/ml) were 50% lower when propylene glycol was used as gavage vehicle instead of saline (2.19±0.94 µg/ml and 9.52±2.52 µg h/ml, respectively). Coefficients‐of‐variation for these parameters were halved in the propylene glycol vehicle however Tmax was unaffected. Ketoconazole increased cyclosporine Cmax and AUC0−6 by 50–60%, regardless of the vehicle or the cyclosporine dose, without altering Tmax (2–3 h). The small effect of ketoconazole suggests that CYP3A‐mediated intestinal and first‐pass hepatic metabolism are minor determinants of cyclosporine oral bioavailability in rats. Copyright © 2002 John Wiley & Sons, Ltd.
Pharmacokinetics of a novel surface‐active agent, purified poloxamer 188, in rat, rabbit, dog and man
Authors: Grindel J. Michael , Jaworski Ted , Emanuele R. Martin , Culbreth Paula 
Published: January 2005

AbstractPurified poloxamer 188 (PP188) is a non‐ionic, block copolymer surfactant that is currently being evaluated clinically in sickle cell disease vaso‐occlusive crisis and acute chest syndrome and preclinically in spinal cord injury and muscular dystrophy. This paper describes the pharmacokinetics of PP188 in rats, pregnant rats, pregnant rabbits, dogs and humans. Plasma protein binding interaction studies demonstrated no clinically significant effects on narcotic analgesics, hydroxyurea, warfarin, diazepam or digitoxin, but an increase in free fraction for propranolol. The plasma concentrations increased proportionate with increasing dose in all species tested. Renal clearance accounted for 90% of total plasma clearance in man. A single metabolite was detected and quantified in the plasma from dogs and humans that was cleared more slowly than parent drug. Allometric scaling of plasma clearance and volume of distribution at steady‐state (Vss) across species provided good predictions of the pharmacokinetic parameters in humans. Based on the comparative pharmacokinetics of PP188 in rat, rabbit, dog and man, all three animal species were appropriate models for evaluating various aspects of PP188's toxicological profile. Copyright © 2002 John Wiley & Sons, Ltd.
Pharmacokinetic changes of diltiazem and desacetyldiltiazem after oral administration of diltiazem in rabbits with diabetes mellitus induced by alloxan
Authors: Choi Jun S. , Kim Yoon G. 
Published: January 2005

AbstractPhysiological changes occurring in diabetes mellitus patients could alter the pharmacokinetics of drugs used to treat hypertension resulting from diabetic complications. Hence, the pharmacokinetics of diltiazem (DTZ) and its metabolite, desacetyldiltiazem (DAD), were investigated after oral administration of DTZ. DTZ, 20 mg/kg, was orally administered to control rabbits and rabbits with fifth day (experiment was performed at fifth day after first and second days intravenous administration of alloxan) and 13th day (experiment was performed at 13th day after first, second, sixth, and 10th days intravenous administration of alloxan) diabetes mellitus induced by alloxan. Impaired kidney and liver functions were observed in both diabetic groups based on plasma chemistry data and/or tissue microscopy. After oral administration of DTZ, the area under the plasma concentration–time curve from time zero to time infinity were 767, 1280 and 1550 ng h/ml for control rabbits and fifth and 13th days diabetes mellitus rabbits, respectively. The values in diabetes mellitus rabbits were significantly different as compared to control rabbits. The terminal half‐lives of DTZ were significantly longer in fifth (13.4 h) and 13th (13.0 h) days diabetes mellitus rabbits than that in control rabbits (8.76 h). The renal clearances of DTZ in fifth (0.316 l/h/kg) and 13th (0.264 l/h/kg) days diabetes mellitus rabbits were significantly slower than that in control rabbits (0.505 l/h/kg), and this could be due to impaired kidney function in the diabetes mellitus rabbits. However, other pharmacokinetic parameters of DAD were not significantly different among three groups of rabbits. Copyright © 2002 John Wiley & Sons, Ltd.
Determinants of the magnitude of willingness to accept relative to willingness to pay
Authors: Shefrin Hersh , Caldwell David 
Published: January 2005

AbstractIn this paper we test two hypotheses that stem from the work of Mellers, Chang, Birnbaum and Ordonez (1992). The first hypothesis is that in a binary gamble, the ratio of WTA to WTP is decreasing in the probability attached to a nonzero event. The second hypothesis is that this ratio is independent of the size of stakes. We find support for the first hypothesis, but mixed support for the second. The second hypothesis holds in the case of gains, but not in the case of losses. Copyright © 2001 John Wiley & Sons, Ltd.
Relating individual differences in Attitude toward Ambiguity to risky choices
Authors: Lauriola Marco , Levin Irwin P. 
Published: January 2005

AbstractSubjects (76 adult Italians of varying ages) completed a two‐part procedure. One part used an Ellsberg‐type task which allowed for both aggregate and individual level analysis of Attitude toward Ambiguity. The other part used an expanded risky choice task to assess the same subjects' Attitude toward Risk. While there was an overall tendency for subjects to be slightly ambiguity‐averse, there was a positive correlation between Attitude toward Ambiguity and Attitude toward Risk. This relation was particularly strong when the risky choice was to avoid a loss rather than to achieve a gain. Copyright © 2001 John Wiley & Sons, Ltd.
Averaging probability judgments: Monte Carlo analyses of asymptotic diagnostic value
Authors: Johnson Timothy R. , Budescu David V. , Wallsten Thomas S. 
Published: January 2005

AbstractWallsten et al. (1997) developed a general framework for assessing the quality of aggregated probability judgments. Within this framework they presented a theorem regarding the effects of pooling multiple probability judgments regarding unique binary events. The theorem states that under reasonable conditions, and assuming conditional pairwise independence of the judgments, the average probability estimate is asymptotically perfectly diagnostic of the true event state as the number of estimates pooled goes to infinity. The purpose of the present study was to examine by simulation (1) the rate of convergence of averaged judgments to perfect diagnostic value under various conditions and (2) the robustness of the theorem to violations of its assumption that the covert probability judgments are conditionally pairwise independent. The results suggest that while the rate of convergence is sensitive to violations of the conditional pairwise independence, the asymptotic properties remain relatively robust under a large variety of conditions. The practical implications of these results are discussed. Copyright © 2001 John Wiley & Sons, Ltd.
Promoting fluency of performance of self‐help tasks with a person with multiple disabilities
Authors: Lancioni Giulio E. , O'Reilly Mark F. , Campodonico Francesca 
Published: January 2005

AbstractA combination of favorite songs and verbal prompts (automatically delivered through portable technology) was used to promote fluency of performance of self‐help tasks in a young man with multiple disabilities. Data indicated that the intervention was effective in reducing the time required by the man to complete the self‐help tasks (dressing and washing). A momentary withdrawal of the prompts after about 6 months from the beginning of the study was accompanied by performance deterioration. Implications of the findings are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
The effects of the Positive Environment Program (PEP) on the behaviors of adults with profound cognitive and physical disabilities
Authors: Realon Rodney E. , Bligen Richard A. , La Force Anne , Helsel William J. , Goldman Vinston 
Published: January 2005

AbstractThis study evaluated the effects of the Positive Environment Program (PEP) on the behaviors of residents and staff in a state‐operated residential facility during a 2½ year period. The participants included 19 adult residents with profound cognitive and physical disabilities and 11 staff members who worked with them. Data were collected on alertness, leisure material availability, engagement, staff interactions, and resident affect during two samples of data collection six months prior to implementation of PEP. Training was then provided to staff on positive interaction skills. Following the training, researchers implemented a monitoring program and a staff incentive program. The results of this project showed improvements in staff interactions, resident interaction with leisure materials, improved levels of alertness, and increases in a ‘happiness index’. The benefits and limitations of this project as well as future research are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
Decreasing rumination using a starchy food satiation procedure
Authors: Dudley Laura L. , Johnson Cammarie , Barnes R. Scott 
Published: January 2005

AbstractA starchy food satiation procedure was evaluated in an ABAB withdrawal design on the post‐meal rumination of a nine‐year‐old girl with autism. During treatment unlimited quantities of starchy foods were provided following each meal. High rates of rumination occurred during baseline conditions, followed by an immediate decrease in rumination during treatment. Rumination decreased to 82 and 97% of baseline during the first and second treatment conditions, respectively. In addition, follow‐up probes were conducted at irregular intervals for 4 years following treatment, during which zero or near‐zero rates of rumination were sustained. This study extends the literature on the functional relation between increased starchy food quantity and rumination in adults to rumination with a young child, and demonstrates maintenance of the treatment effect for 4 years. Copyright © 2002 John Wiley & Sons, Ltd.
Collateral effects of behavioral parent training on families of children with developmental disabilities and behavior disorders
Authors: Feldman Maurice A. , Werner Shannon E. 
Published: January 2005

AbstractWe evaluated collateral effects of behavioral parent training (BPT) on families with children who have developmental disabilities and behavior disorders. We compared 18 BPT graduates to 18 similar families waiting for service. The BPT graduates reported significantly less (i) child behavior problems, (ii) disruption to child and family quality of life due to child problem behavior, and (iii) stress related to limits on family opportunities and child physical limitations, up to 5 years after discharge. On a self‐efficacy scale, the graduates reported being more effective child behavior change agents in not only stopping child problem behavior, but also in preventing new occurrences and teaching the child appropriate behavior. These results suggest that BPT has persistent beneficial effects on children and parents. The findings reflect the program's focus on teaching parents how to use functional assessment derived positive teaching strategies to replace child problem behavior. Copyright © 2002 John Wiley & Sons, Ltd.
Rapid expression of vaccine proteins for B‐cell lymphoma in a cell‐free system
Authors: Yang Junhao , Kanter Gregory , Voloshin Alexei , Michel‐Reydellet Nathalie , Velkeen Hendrik , Levy Ronald , Swartz James R. 
Published: January 2005

AbstractThe idiotype (Id)‐granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) fusion proteins are potential vaccines for immunotherapy of B‐cell lymphoma. In this study, four vaccine candidates were constructed by fusing murine GM‐CSF to the amino‐ or carboxy‐terminus of the 38C13 murine B‐lymphocyte Id scFv with two different arrangements of the variable regions of the heavy chain and light chain (VL‐VH and VH‐VL). scFv (VH‐VL) and GM‐CSF/scFv fusion proteins were expressed in an Escherichia coli cell‐free protein synthesis system. In order to promote disulfide bond formation during cell‐free expression, cell extract was pretreated with iodoacetamide (IAM), and a sulfhydryl redox buffer composed of oxidized and reduced glutathione was added. The E. coli periplasmic disulfide isomerase, DsbC, was also added to rearrange incorrectly formed disulfide linkages. The 38C13 B‐lymphocyte Id scFv was expressed with 30% of its soluble yield in active form (43 μg/ml) when tested with an anti‐idiotypic mAb, S1C5, as the capture antibody in radioimmunoassay. It was found that the amino‐terminal GM‐CSF fusion proteins, GM‐VL‐VH and GM‐VH‐VL, showed much higher activity than the carboxy‐terminal GM‐CSF fusion proteins, VL‐VH‐GM and VH‐VL‐GM, in stimulating the cell proliferation of a GM‐CSF‐dependent cell line, NFS‐60. Between the two amino‐terminal GM‐CSF fusion proteins, GM‐VL‐VH showed a higher total and soluble yield than GM‐VH‐VL. © 2005 Wiley Periodicals, Inc.
Selection of high‐producing CHO cells using NPT selection marker with reduced enzyme activity
Authors: Sautter Kerstin , Enenkel Barbara 
Published: January 2005

AbstractWe developed an expression system that aimed to increase the proportion of high producers in a transfected cell population in order to reduce the effort in clone screening. The principle is based on the impairment of the selection marker. Twelve single‐point mutations in more or less conserved domains of the resistance marker gene neomycin‐phosphotransferase (NPT) resulted in different degrees of reduced enzyme activity, depending on the amino acid conservation and the kind of amino acid exchange. In all transfected, mutant‐NPT bearing CHO‐DG44 cell pools surviving the selection with G418, the ratio of high‐producing cells to total cell number was higher than in pools selected with wildtype‐NPT. Furthermore, these pools showed, in comparison to wildtype‐NPT selected pools, not only higher NPT‐RNA levels but also increased specific productivities and higher titers of a coexpressed biopharmaceutically relevant product. Elevated productivity could be ascribed to higher gene copy numbers, integration into chromatin regions with higher transcriptional activity, or a combination of both effects. Thus, the use of NPT‐mutants as selection markers is suitable for the enrichment of high producers in a transfected CHO‐DG44 cell population, since cell survival is achieved only if the enzymatic impairment of the cointegrated resistance marker is compensated by a higher expression level. © 2005 Wiley Periodicals, Inc.