bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abacavir: Absolute Bioavailability, Bioequivalence of Three Oral Formulations, and Effect of Food
Authors: Chittick Gregory E. , Gillotin Catherine , McDowell James A. , Lou Yu , Edwards Kathleen D. , Prince William T. , Stein Daniel S. 
Published: May 2004

Study Objectives. Study A: to determine the absolute bioavailability of a single 300‐mg abacavir hemisulfate tablet. Study B: to determine the bioequivalence of two oral abacavir formulations (300‐mg hemisulfate tablet, 100‐mg succinate caplet), the effect of food on the bioavailability of the 300‐mg hemisulfate tablet, and the bioavailability of the hemisulfate tablet relative to the hemisulfate solution.Design. Phase I, randomized, open‐label, balanced two‐ (study A) and three‐or four‐period (study B), crossover studies.Setting. Two clinical research centers.Subjects. Six men infected with the human immunodeficiency virus (HIV), aged 27–39 years (study A), and 18 HIV‐infected men and women, aged 21–50 years (study B).Interventions. In study A, all subjects received a single, oral 300‐mg tablet of abacavir hemisulfate or a single, intravenous infusion of abacavir hemisulfate 150 mg over 60 minutes. In study B, all subjects received each of three single‐dose treatments: three 100‐mg abacavir succinate caplets in a fasted state, one 300‐mg abacavir hemisulfate tablet in a fasted state, and one 300‐mg abacavir hemisulfate tablet with a high‐fat breakfast. Twelve subjects in study B also received a fourth treatment of abacavir hemisulfate 300 mg as an oral solution in a fasted state. Plasma samples collected for 24 hours (study A) or 12 hours (study B), and urine samples collected for 12 hours (study A) were analyzed by validated high‐performance liquid chromatographic methods.Measurements and Main Results. Abacavir pharmacokinetic parameters were calculated using standard, noncompartmental methods. In study A, the geometric least square (GLS) mean absolute bioavailability of oral abacavir was 83% (range 65–107%). In study B, the hemisulfate tablet was bioequivalent to the succinate caplet, but its time to maximum concentration (Tmax) occurred 30 minutes earlier. Administration of the abacavir hemisulfate tablet with food had no effect on area under the curve from time zero to infinity (AUC0–∞), decreased maximum concentration (Cmax) by 26%, and delayed Tmax by 38 minutes. The relative bioavailability (GLS mean AUC0–∞ ratio) of the 300‐mg abacavir hemisulfate tablet to solution was 101%, Cmax was 11% lower, and Tmax was unchanged. The most common drug‐related adverse events associated with abacavir were nausea, vomiting, abdominal pain, and headache, all of which were mild.Conclusion. Based on our results, abacavir is safe and well tolerated and can be administered with or without meals.
Comparison of Iothalamate Clearance Methods for Measuring GFR
Authors: Dowling Thomas C. , Frye Reginald F. , Fraley Donald S. , Matzke Gary R. 
Published: May 2004

Study Objective. To evaluate the bias and precision of three methods of measuring glomerular filtration rate (GFR) relative to a standard method.Design. Prospective, outpatient study.Setting. University‐affiliated general clinical research center.Patients. Twenty‐six patients with various degrees of renal function (GFR range 25–151 ml/min/1.73 m2).Interventions. Each patient received iothalamate twice during the study visit, first as a bolus injection and then as a priming dose followed by a constant‐rate infusion for 2.5 hours.Measurements and Main Results. Plasma (ClpIVB) and renal clearances (ClrIVB) after bolus injection and plasma clearance during constant‐rate infusion (ClpINF) were compared with standard renal clearance during constant‐rate infusion (ClrINF). All three measures were highly correlated with ClrINF (r>0.90, p<0.001). The mean ClrIVB was not significantly different from ClrINF (106.3 ± 30.4 vs 104.2 ± 28.5 ml/min/1.73 m2) and provided a precise (8.8%, 95% CI 6.5–11.1%) and unbiased measure of GFR. Both ClpIVB and ClpINF were positively biased; values exceeded ClrINF by 11.8 ± 11.1 (p=0.0001) and 10.5 ± 12.5 ml/min/1.73 m2 (p=0.0003), respectively. Use of a nonrenal correction factor of 9.8 and 10.5 ml/min/1.73 m2 for infusion and bolus plasma clearance values, respectively, eliminated bias and improved the precision of these methods.Conclusions. Iothalamate renal clearance after bolus injection is a simple, accurate, and precise measurement of GFR and may be a useful alternative to the standard infusion method in clinical investigations. The corrected plasma clearance provides a simple index of GFR for clinical practice.
Atovaquone Suspension in HIV‐Infected Volunteers: Pharmacokinetics, Pharmacodynamics, and TMP‐SMX Interaction Study
Authors: Falloon Judith , Sargent Susie , Piscitelli Stephen C. , Bechtel Christine , LaFon Stephen W. , Sadler Brian , Walker Robert E. , Kovacs Joseph A. , Polis Michael A. , Davey Richard T. , Lane H. Clifford , Masur Henry 
Published: May 2004

Study Objective. To evaluate the pharmacokinetics and safety of atovaquone suspension in volunteers infected with the human immunodeficiency virus ((HIV).Design. Open‐label, nonrandomized study.Setting. Two clinical research centers.Patients. Twenty‐two HIV‐infected volunteers with a median CD4 cell count of 37 cells/mm3.Interventions. Patients received atovaquone suspension fasting or fed for 2‐week periods with crossover at dosages of 500 mg/day, and randomization to fasting or fed at dosages of 750 and 1000 mg/day. A subset of patients also received 750 mg twice/day with food, and a subset of those who received 1000 mg/day fasting also received 1000 mg with food. During a long‐term dosing phase, a subset of subjects were evaluated for an interaction between atovaquone and trimethoprim‐sulfamethoxazole (TMP‐SMX).Measurements and Main Results. Average steady‐state atovaquone concentrations at 500 mg were 6.7 ± 3.2 μg/ml fasted and 11.3 ± 5.0 μg/ml with food; at 750 mg, 9.9 ± 7.1 μg/ml fasted and 12.5 ± 5.9 μg/ml with food; at 1000 mg, 9.7 ± 4.3 μg/ml fasted and 13.6 ± 5.0 μg/ml with food; and at 1500 mg, 21.1 ± 5.0 μg/ml with food. Thus, plasma concentrations were not proportional to dose. Concomitant food ingestion resulted in a 1.3‐ to 1.7‐fold increase in values. Average steady‐state concentrations were less than 10 μg/ml in 21% and more than 15 μg/ml in 36% of patients at 1000 mg/day with food; at 750 mg twice/day, all five patients had levels above 15 μg/ml. Atovaquone suspension was well tolerated; diarrhea, nausea, fatigue, and rash were the most common adverse events. Concomitant administration of TMP‐SMX did not change atovaquone concentrations and resulted in small decreases in concentrations of TMP (16%) and SMX (10%).Conclusion. Plasma concentrations are significantly higher when atovaquone suspension is administered with food compared with fasting. Total doses of 1500 mg/day are likely to achieve concentrations effective for prophylaxis of Pneumocystis carinii pneumonia.
CYP2D6 Mutations and Therapeutic Outcome in Schizophrenic Patients
Authors: Hamelin Bettina A. , Dorson Peter G. , Pabis Dennis , Still Daniel , Bouchard Roch‐H. , Pourcher Emmanuel , Rail Jimmy , Turgeon Jacques , Crismon M. Lynn 
Published: May 2004

Study Objective. To investigate whether a relationship exists between the most common known cytochrome P450 (CYP) isozyme 2D6 mutations and schizophrenia. Because most antipsychotic and antidepressant agents interact with CYP2D6, we also investigated clinical outcomes in schizophrenic poor metabolizers (PMs) and extensive metabolizers (EMs).Design. Prospective, observational study.Setting. Two psychiatric hospitals and a university‐affiliated nonpsychiatric hospital.Subjects. Thirty‐nine consecutive schizophrenic patients (POP 1), 89 schizophrenics of French Canadian origin (POP 2), and 384 healthy French Canadians (POP 3).Intervention. All study subjects were genotyped for CYP2D6 mutant alleles. POP 1 patients were evaluated before and after 21 or more days of treatment with antipsychotic drugs metabolized at least in part by CYP2D6.Measurements and Main Results. Whole blood was collected to determine CYP2D6 alleles *1, *3, *4, *5, *6, and *7 using standard restriction fragment length polymorphisms and polymerase chain reaction techniques. In comparison, CYP2D6 genotypes were determined in POP 2 and POP 3. Twenty‐three (59.0%) of 39 patients in POP 1 were genotypically EM homozygotes, 15 (38.4%) were EM heterozygotes, and 1 (2.6%) was a PM. Similar genotype distributions were determined in POP 2 and in POP 3. Genotype distributions for all three populations were in Hardy‐Weinberg equilibrium (p>0.05), and there was no significant difference among them (p=0.857). In POP 1, no differences were seen among genotypes in disease symptom severity, number and severity of adverse drug effects, or attitudes toward drug treatment at baseline and at the end of the study. In fact, all patients improved significantly during their hospital stay (all p<0.05), although independent of the CYP2D6 genotype.Conclusion. Common CYP2D6 mutant alleles were not associated with schizophrenia or with disease symptoms, antipsychotic‐related adverse effects, or attitudes toward treatment.
Pharmacokinetics and Protein Binding of Eprosartan in Hemodialysis‐Dependent Patients with End‐Stage Renal Disease
Authors: Kovacs Steven J. , Tenero David M. , Martin David E. , Ilson Bernard E. , Jorkasky Diane K. 
Published: May 2004

Study Objectives. To compare eprosartan pharmacokinetics in hemodialysis patients and in volunteers with normal renal function, and to determine the effect of hemodialysis on these values.Design. Open‐label, parallel‐group, single‐dose study.Setting. Outpatient hemodialysis treatment center and an industry‐affiliated clinical pharmacology unit.Patients. Ten healthy volunteers and nine hemodialysis patients.Intervention. A single oral dose of eprosartan 400 mg was administered to volunteers on 1 day and to patients on 2 days (a nondialysis and a dialysis day). Patients underwent high‐flux hemodialysis.Measurements and Main Results. Concentrations of eprosartan in plasma and dialysate were assayed by high‐performance liquid chromatography; plasma protein binding was determined by ultrafiltration. Eprosartan pharmacokinetics showed greater variability in patients than in volunteers. However, six of nine patients had exposures that were within the range observed for volunteers. Mean total AUC0–t was increased approximately 60% (95% CI −22, 225) in patients. Total Cmax was similar between groups (PE = 1.01, 95% CI −40, 71). Mean percent fraction unbound (%fu) in patients (3.02%) was significantly greater than that in volunteers (1.74%). Unbound AUC0–t and unbound Cmax were, on average, approximately 172% (95% CI 28, 479) and 73% (95% CI −1, 199) greater, respectively, in patients. After hemodialysis, the mean %fu decreased from 3.19–2.01%. Mean recovery of eprosartan in dialysate was 6.8 mg (range 0–23.1 mg) and hemodialytic clearance was approximately 11 ml/minute, which does not represent a significant portion of total clearance.Conclusions. Eprosartan was safe and well tolerated in both groups. Based on its known safety profile and because of its exaggerated pharmacokinetic variability in patients undergoing hemodialysis, treatment should be individualized based on tolerability and response. Supplemental doses of eprosartan after hemodialysis are unnecessary.
A Pilot Study of the Efficacy of Constant‐Infusion Ceftazidime in the Treatment of Endobronchial Infections in Adults with Cystic Fibrosis
Authors: Bosso John A. , Bonapace Charles R. , Flume Patrick A. , White Roger L. 
Published: May 2004

Study Objective. To compare the efficacy of constant‐infusion ceftazidime (CTZ) with that of traditional intermittent dosing in a pilot trial.Design. Prospective, crossover trial.Subjects. Five adults with cystic fibrosis requiring intravenous antibiotic therapy for pulmonary exacerbations of the disease.Interventions. Patients were initially treated with standard CTZ 2 g 3 times/day for 10 days. At the next hospitalization patients were crossed over and CTZ was administered as a constant infusion at a rate determined to achieve a serum concentration 6.6 times the minimum inhibitory concentration (MIC) of the least susceptible Pseudomonas aeruginosa isolate.Measurements and Main Results. The pharmacokinetics of CTZ were determined, as were MICs for all P. aeruginosa isolates. Outcome parameters of interest were changes with therapy in white blood cell count, P. aeruginosa density in sputum, and pulmonary function test results. Differences in these parameters for the two forms of administration were not significant. With the exception of one patient who received 6 g/day with both regimens, the average reduction in dosage with the constant infusion was 50%.Conclusion. These preliminary data suggest that constant‐infusion CTZ may be as safe and efficacious as intermittent dosing.
Indinavir Concentrations and Antiviral Effect
Authors: Acosta Edward P. , Henry Keith , Baken Leslie , Page Linda M. , Fletcher Courtney V. 
Published: May 2004

Study Objectives. To determine the variability of indinavir pharmacokinetics in patients attending an outpatient clinic, and to explore relationships between indinavir exposure and antiviral effect.Design. Open, formal pharmacokinetic evaluation.Setting. University‐affiliated clinical research center.Patients. Forty‐three adults infected with the human immunodeficiency virus (HIV) receiving therapy with indinavir and concomitant nucleoside reverse transcriptase inhibitors.Intervention. Indinavir concentrations were measured after patients were observed taking an 800‐mg oral dose, and pharmacokinetic parameters were determined using a one‐compartment oral absorption model. Virologic and pharmacologic characteristics were compared in a subset of 23 patients who were protease inhibitor naïve before receiving indinavir.Measurements and Main Results. Mean indinavir pharmacokinetics were similar to those reported previously. Significant intersubject variability in systemic exposure was observed in patients receiving the same dosage; the 8‐hour area under the curve (AUC8) ranged from 5.4–68.0 μM•hour. In protease inhibitor‐naïve subjects, the indinavir AUC8 was statistically higher in those with undetectable plasma HIV RNA (30.7 μM•hr) versus detectable plasma HIV RNA (22.4 μM•hr, p=0.035). Measured concentrations 5 hours after the dose and extrapolated 8‐hour concentrations were also significantly higher in patients with undetectable plasma HIV RNA (both p=0.007).Conclusions. Indinavir plasma concentrations were highly variable among patients receiving the same dosage. Patients with an undetectable plasma HIV RNA level who were protease inhibitor naïve had statistically higher indinavir concentrations and slower oral clearance than the group with detectable HIV RNA. Relationships between indinavir concentrations and anti‐HIV effect provide a basis for quantifying the pharmacologic contribution to the heterogeneity in therapeutic response.
Safety and Efficacy of 4‐Aminopyridine in Humans with Spinal Cord Injury: A Long‐Term, Controlled Trial
Authors: Segal Jack L. , Pathak Mayank S. , Hernandez Jesus P. , Himber Peter L. , Brunnemann Sherry R. , Charter Richard S. 
Published: May 2004

Study Objective. To determine the effects of the long‐term administration of 4‐aminopyridine (4‐AP) on sensorimotor function in humans with longstanding spinal cord injury (SCI).Design. Randomized, open‐label, active‐treatment control, dosage‐blinded study.Setting. University‐affiliated, tertiary‐level care, Department of Veterans Affairs Medical Center.Patients. Twenty‐one healthy men and women outpatients suffering from traumatic SCI (14 tetraplegic, 7 paraplegic) for 2 years or more.Interventions. Dosages of an immediate‐release formulation of 4‐AP were titrated. At 3 months, 16 subjects were receiving 4‐AP 30 mg/day (high dose); 5 subjects were receiving 4‐AP 6 mg/day (low dose) and served as an active‐treatment control group.Measurements and Main Results. Composite motor and sensory scores had statistically significant increases at 3 months. Maximal expiratory pressure, maximal inspiratory pressure, forced vital capacity, and forced expiratory volume in 1 second showed clinically meaningful and/or statistically significant increases among patients receiving 4‐AP 30 mg/day. These subjects also had significant decreases in spasticity (modified Ashworth Scale). Serial biochemical profiles and electroencephalographs were unchanged from baseline, and no clinically significant drug toxicity was encountered.Conclusions. Long‐term oral administration of immediate‐release 4‐AP was associated with improvement in and recovery of sensory and motor function, enhanced pulmonary function, and diminished spasticity in patients with long‐standing SCI. 4‐Aminopyridine appears to be safe and relatively free from toxicity when administered orally over 3 months. Each patient who received immediate‐release 4‐AP 30 mg/day showed a response in one or more of the outcome measures.
Efficacy and Cost of Ampicillin‐Sulbactam and Ticarcillin‐Clavulanate in the Treatment of Hospitalized Patients with Bacterial Infections
Authors: McKinnon Peggy S. , Neuhauser Melinda M. 
Published: May 2004

Study Objective. To evaluate the efficacy and cost of treatment with two β‐lactam/β‐lactamase‐inhibitor combinations.Design. Retrospective, open‐label multicenter study.Setting. Fifty‐four hospitals across the United States.Patients. Eight hundred ninety patients with skin and soft tissue, intraabdominal, gynecologic, respiratory, urinary tract, or other infections that required parenteral antibiotic therapy.Intervention. Patients were administered either ampicillin‐sulbactam 1.5 or 3.0 g every 6 hours or ticarcillin‐clavulanate 3.1 g every 6 hours.Measurements and Main Results. The agents did not differ significantly in efficacy for most infections; although, ampicillin‐sulbactam was bacteriologically superior to ticarcillin‐clavulanate in the treatment of intraabdominal infections (p=;0.0011). Costs of ampicillin‐sulbactam, particularly the 1.5‐g dose, were lower than those of ticarcillin‐clavulanate for skin and soft tissue (p<0.001), intraabdominal (p=;0.005), and respiratory tract (p<0.001) infections.Conclusion. Ampicillin‐sulbactam provides effective coverage for patients with the above infections and is as effective as the broader‐spectrum agent.
Comparison of a Neural Network Approach with Five Traditional Methods for Predicting Creatinine Clearance in Patients with Human Immunodeficiency Virus Infection
Authors: Herman Ronald A. , Noormohamed Saleem , Hirankarn Sarapee , Shelton Mark J. , Huang Eric , Morse Gene D. , Hewitt Ross G. , Stapleton Jack T. 
Published: May 2004

Study Objective. To compare the results of an artificial neural network approach with those of five published creatinine clearance (Clcr) prediction equations and with the measured (true) Clcr in patients infected with the human immunodeficiency virus (HIV).Design. Six‐month prospective study.Settings. Two university medical centers.Patients. Sixty‐five HIV‐infected patients: 18 relatively healthy outpatients and 47 inpatients.Interventions. All subjects had urine collected for 24 hours to determine Clcr.Measurements and Main Results. The 16 input variables were age, ideal body weight, actual body weight, body surface area, height, and the following blood chemistries: sodium, potassium, aspartate aminotransferase, alanine aminotransferase, red blood cell count, platelet count, white blood cell count, glucose, serum creatinine, blood urea nitrogen, and albumin. The only output variable was Clcr. A training set of 55 subjects was used to develop the relationship between input variables and the output variable. The trained neural network was then used to predict Clcr of a validation set of 10 subjects. Mean differences between predicted Clcr and actual Clcr (bias) were 4.1, 28.7, 29.4, 26.0, 31.8, and 55.8 ml/min/1.73 m2 for the artificial neural network, Cockcroft and Gault, Jelliffe 1, Jelliffe 2, Mawer et al, and Hull et al methods, respectively.Conclusion. The accuracy of predicting Clcr in subjects with HIV infection by the artificial neural network is superior to that of the five equations that are currently used in clinical settings.
Monitoring Unfractionated Heparin Therapy with Antifactor Xa Activity Results in Fewer Monitoring Tests and Dosage Changes than Monitoring with the Activated Partial Thromboplastin Time
Authors: Rosborough Terry K. 
Published: May 2004

Study Objective. To determine how much more costly it is to monitor unfractionated heparin (UFH) therapy by antifactor Xa heparin activity (HA) than by activated partial thromboplastin time (aPTT).Design. Prospective, randomized, unmasked, cohort, single‐center study.Setting. A 625‐bed, adults‐only, private teaching hospital.Patients. Two hundred sixty‐eight patients with a variety of indications for UFH therapy.Interventions. Patients were treated with UFH based on ideal weight (75 U/kg bolus, 20 U/kg initial infusion) and monitored by either HA or aPTT.Measurements and Main Results. After adjusting for gender, groups were equivalent in patient characteristics and UFH dosage. The HA group had fewer monitoring tests and dosage changes/24 hours than the aPTT group. These reductions neutralized much of the increased cost of the HA assay itself.Conclusion. Monitoring UFH therapy over 96 hours with an HA assay costs $4.37 more than monitoring with aPTT. This modest increase may be acceptable given other advantages of the HA assay.
Albumin Use in Neurosurgical Critical Care
Authors: Varney Kimberly L. , Young Byron , Hatton Jimmi 
Published: May 2004

Study Objective. To examine the use of albumin in patients receiving neurosurgical intensive care.Design. Survey and chart review of albumin use in neurosurgical intensive care units.Setting. University of Kentucky Chandler Medical Center and American Brain Injury Consortium (ABIC).Subjects. Thirty‐eight patients who underwent neurosurgery at the University of Kentucky Chandler Medical Center; members of the ABIC.Interventions. Chart review with attention to administration of albumin; mailed survey to 200 ABIC members.Measurements and Main Results. Patients admitted to the neurosurgical intensive care unit at the University of Kentucky Chandler Medical Center over a 6‐month interval were evaluated. Albumin, either 5% or 25%, was prescribed for approximately 25% of patients. The indications for use were vasospasm and maintenance of cerebral perfusion pressure. The response rate for the ABIC survey was 39%. Respondents stated that normal saline and albumin were both primary fluid choices for the treatment of vasospasm. Twenty‐two percent reported a reduction in albumin prescribing following a formal warning statement issued by the Food and Drug Administration regarding the use of albumin in critically ill patients.Conclusions. Chart review revealed the primary indications for albumin in the neurosurgical intensive care unit, and our survey data demonstrated the lack of consensus among neurosurgeons regarding their fluid of choice for neurosurgery indications. Prospective, randomized investigations comparing colloids to crystalloids in patients receiving neurosurgical intensive care are required to help define the role of albumin in neurosurgery patients.