bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of First‐Time Idiopathic Seizures in Users of Tramadol
Authors: Gasse Ms. Christiane , Derby Laura , Vasilakis‐Scaramozza Catherine , Jick Hershel 
Published: June 2004

Study Objective. To assess the risk of idiopathic incident seizures among patients who ever took tramadol.Design. Nested case‐control design.Setting. General Practice Research Database from November 1996–August 1998.Patients. Eleven thousand three hundred eighty‐three patients.Intervention. Comparison of risks of idiopathic incident seizures during exposed and unexposed times among patients who had ever taken tramadol and other analgesics with 90‐day follow‐up.Measurements and Main Results. Among the 11,383 subjects we identified 21 cases of idiopathic seizures, 10 of which were categorized as definite cases and 11 categorized as possible cases. Three patients were exposed to tramadol alone in the previous 90 days, 10 to opiates, three to both tramadol and opiates, one to other analgesics, and four to no analgesics.Conclusion. The risk of idiopathic seizures was similarly elevated in each analgesic exposure category compared with nonusers, suggesting that the risk for patients taking tramadol was not increased compared with other analgesics.(Pharmacotherapy 2000; 20(6):629–634)
Comparison of the Serum and Intracellular Pharmacokinetics of Azithromycin in Healthy and Diabetic Volunteers
Authors: Ernst Erika J. , Klepser Michael E. , Klepser Teresa B. , Nightingale Charles H. , Hunsicker Lawrence G. 
Published: June 2004

Study Objective. To compare serum and intracellular pharmacokinetics of azithromycin in healthy volunteers and patients with diabetes.Design. Open‐label, parallel study.Setting. Clinical research center.Subjects. Twelve patients with diabetes and 12 healthy volunteers.Interventions. Subjects were given a single 500‐mg dose of azithromycin followed by 250 mg/day for 2 days. Blood samples were obtained just before and after the third dose for up to 24 hours for serum and 168 hours for intracellular measurement of azithromycin.Measurements and Main Results. Pharmacokinetic parameters were calculated by noncompartmental methods and compared with a t test. The groups did not differ in maximum concentration, time to maximum concentration, or area under the concentration‐time curve in serum or polymorphonuclear cells (PMNs). Differences in the PMN:serum ratio were observed at the 24‐hour time point (healthy 1209 ± 432, diabetic 859 ± 286, p= 0.051).Conclusion. In general, the pharmacokinetics of azithromycin are comparable in diabetics and healthy volunteers. Accumulation of drug in macrophages was slightly lower in patients.
Comparative In Vitro Activity of Vancomycin and Levofloxacin in Combination with Rifampin Against Planktonic versus Sessile Cells of Staphylococcus epidermidis
Authors: Kang‐Birken S. Lena 
Published: June 2004

Study Objective. To evaluate the activity of vancomycin and levofloxacin alone and combined with rifampin against planktonic and sessile cells.Intervention. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of the three drugs were determined against a clinical isolate of methicillin‐resistant Staphylococcus epidermidis (MRSE 23) and a reference strain of MRSE (ATCC 35984).Measurements and Main Results. The MICs/MBCs of vancomycin, levofloxacin, and rifampin against MRSE 23 were 0.78/0.78 μg/ml, 0.19/0.19 μg/ml or below, and 0.19/0.19 μg/ml or below, and against ATCC 35984 were 0.78/1.56 μg/ml, 0.19/0.19 μg/ml or below, and 0.19/0.19 μg/ml or below, respectively. A 99.9% killing activity was achieved with vancomycin, levofloxacin, and vancomycin‐levofloxacin against planktonic cells of MRSE 23 (18.9, 21.3, and 17.5 hrs, respectively) and only with levofloxacin against ATCC 35984 (21.5 hrs). No regimen achieved 99.9% killing activity against sessile cells.Conclusion. Adding rifampin was antagonistic against planktonic cells and had an additive effect against sessile cells. Activity typically reported using nutrient‐rich, planktonic cells may not be applicable to sessile cells under environmental and growth restrictions.
A Dose‐Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous Gatifloxacin in Healthy Adult Men
Authors: Gajjar Diptee A. , LaCreta Frank P. , Uderman Howard D. , Kollia Georgia D. , Duncan Glenn , Birkhofer Martin J. , Grasela Dennis M. 
Published: June 2004

Study Objectives. To examine single‐ and multiple‐dose safety, tolerability and pharmacokinetics of gatifloxacin administered as daily 1‐hour intravenous infusions for 14 days, and to determine the effect of gatifloxacin on glucose tolerance, pancreatic β‐cell function, and electrocardiogram (ECG).Design. Randomized, double‐blind, placebo‐controlled, ascending‐dose study.Setting. Bristol‐Myers Squibb, Clinical Pharmacology Unit, Princeton, New Jersey, USA.Patients. Forty healthy male subjects, eight in each of five groups, were enrolled to receive sequential doses of gatifloxacin: 200 mg (10 mg/ml), 200 mg (1 mg/ml), and 400, 600, and 800 mg (2 mg/ml); six subjects per group received active drug and two received placebo.Interventions. A single dose of the drug was administered as an intravenous infusion over 1 hour. After a 72‐hour washout period, the drug was administered once/day for 14 days by 1‐hour intravenous infusion. Physical examinations, ECGs, spirometry, and clinical laboratory tests, including glucose tolerance test (GTT) and assessment of glucose homeostasis, were performed before treatment and on selected dosing days. A safety evaluation was performed before escalating doses. No intrasubject dose escalation was permitted.Measurements and Main Results. The pharmacokinetics of gatifloxacin were dose linear and time independent after intravenous administration over the range of 200–800 mg. After daily repeated administration, a predictable, modest accumulation was observed; steady state was reached by the third dose. Approximately 80% of the dose was recovered as unchanged drug in urine. Mean changes (before the first dose to the last dose) after oral GTT and in fasting serum glucose, insulin, and C‐peptide concentrations were comparable among the gatifloxacin and placebo treatment groups. A mild, transient decrease in serum glucose was associated with the end of the 1‐hour infusion of gatifloxacin. No clinically important changes in QTc interval or spirometry occurred. The most frequent treatment‐related adverse effects were local intravenous site reactions, which were associated with dose and/or concentration of intravenous solution.Conclusion. Gatifloxacin was safe and well tolerated at intravenous doses of up to 800 mg/day for 14 days. Gatifloxacin pharmacokinetics were linear and time independent.
Interchangeability of 400‐mg Intravenous and Oral Gatifloxacin in Healthy Adults
Authors: LaCreta Frank P. , Kaul Sanjeev , Kollia Georgia D. , Duncan Glenn , Randall Dianne M. , Grasela Dennis M. 
Published: June 2004

Study Objective. To evaluate the interchangeability of 400‐mg intravenous and oral doses of gatifloxacin.Design. Randomized, open‐label, crossover study.Setting. GFI Pharmaceutical Services, Inc., Evansville, Indiana, USA.Subjects. Twenty‐four healthy men and women (12 of each gender), aged 18–42 years.Interventions. Subjects received single doses of gatifloxacin 400 mg either by intravenous infusion over 1 hour or a 400‐mg tablet orally with 240 ml of water, each dose separated by a 1‐week washout. Plasma concentrations of gatifloxacin were determined by a validated high‐performance liquid chromatography; pharmacokinetic parameters were calculated using noncompartmental methods. Distributions of pharmacokinetic parameter values were summarized by route of administration and gender. Effects of treatment on pharmacokinetic parameter values of gatifloxacin were assessed by an analysis of variance model suitable for a two‐way, two‐treatment, crossover design. Clinical evaluations were performed to assess drug safety and tolerability.Measurements and Main Results. Intravenous and oral gatifloxacin were considered interchangeable because both routes were bioequivalent with respect to area under the curve (AUC; 90% confidence interval for the ratio of geometric means contained within 0.8–1.25). The plasma concentration‐time profile after intravenous administration was similar and comparable in extent of exposure (AUC0–∞) with that for the oral route when equal doses were administered to men and women. The absolute bioavailability of gatifloxacin after oral administration was 96%, consistent with bioequivalence of the 400‐mg intravenous and oral doses. The drug was well tolerated; the frequency of adverse events was comparable after intravenous and oral administration.Conclusion. Intravenous and tablet formulations of gatifloxacin are bioequivalent and therefore interchangeable. This permits greater flexibility in choosing oral or parenteral therapy, with the possibility of avoiding hospitalization based on knowledge that oral administration will deliver therapeutic exposure to the drug, or abbreviating hospital stay due to ease of switching from intravenous to oral therapy.
Effect of Multiple‐Dose Gatifloxacin or Ciprofloxacin on Glucose Homeostasis and Insulin Production in Patients with Noninsulin‐Dependent Diabetes Mellitus Maintained with Diet and Exercise
Authors: Gajjar Diptee A. , LaCreta Frank P. , Kollia Georgia D. , Stolz Randall R. , Berger Sheldon , Smith William B. , Swingle Mary , Grasela Dennis M. 
Published: June 2004

Study Objectives. To compare the effects of gatifloxacin and ciprofloxacin on glucose homeostasis, including glucose tolerance test (GTT), pancreatic β‐cell function, and insulin production and secretion in patients with noninsulin‐dependent (type 2) diabetes mellitus (NIDDM) maintained with diet and exercise; and to evaluate the pharmacokinetics, safety, and tolerability of gatifloxacin.Design. Randomized, double‐blind, placebo‐controlled, multiple‐dose study.Setting. GFI Pharmaceutical Services, Inc., Evansville, Indiana; Chicago Center for Clinical Research, Chicago, Illinois; and New Orleans Center for Clinical Research, New Orleans, Louisiana, USA.Patients. Forty‐eight men and women with NIDDM.Interventions. Patients were assigned sequentially at enrollment to receive gatifloxacin 400 mg/day orally, ciprofloxacin 500 mg twice/day orally, or placebo for 10 days. Oral GTTs were performed on specific days throughout the study, as well as measurements of serum glucose, serum insulin, and C‐peptide levels. Physical examinations, electrocardiograms, spirometry, and clinical laboratory tests were performed before dosing and on selected dosing days.Measurements and Main Results. Gatifloxacin had no significant effect on glucose tolerance and pancreatic β‐cell function, as shown by oral GTT results and insulin and C‐peptide levels. Fasting glucose levels 0–6 hours after gatifloxacin administration on days 1 and 10 showed a downward trend, but it was not significant compared with placebo; results were similar with ciprofloxacin. Gatifloxacin also lacked a long‐term effect on fasting insulin levels, but this was not shown for a short‐term effect, suggesting a modest, transient effect on insulin release. On the other hand, ciprofloxacin had no short‐term effect but produced a more sustained effect on insulin release and production. The pharmacokinetics of gatifloxacin in patients with NIDDM were similar to those in healthy subjects. Overall, subjects tolerated treatment well. All reported drug‐related adverse events were mild to moderate in intensity. The frequency of adverse events was similar in gatifloxacin‐ and ciprofloxacin‐treated patients, and only slightly higher than in placebo‐treated patients.Conclusion. Gatifloxacin was well tolerated in patients with NIDDM controlled by diet and exercise. It had no significant effect on glucose homeostasis, β‐cell function, or long‐term fasting serum glucose levels, but it did cause a brief increase in serum insulin levels.
Safety and Pharmacokinetics of a Single Oral Dose of Gatifloxacin in Patients with Moderate to Severe Hepatic Impairment
Authors: Grasela Dennis M. , Christofalo Barbara , Kollia Georgia D. , Duncan Glenn , Noveck Robert , Manning James A. , LaCreta Frank P. 
Published: June 2004

Study Objectives. To assess the safety and pharmacokinetics of oral gatifloxacin 400 mg in subjects with and without hepatic impairment, and the need to modify doses in patients with hepatic dysfunction.Design. Single‐dose, nonrandomized, open‐label, parallel‐group study.Setting. Clinical Research Center, New Orleans, Louisiana.Patients. Eight subjects with grade B or C hepatic dysfunction (Child‐Pugh classification) and eight age‐, weight‐, and gender‐matched subjects with normal hepatic function.Interventions. After a single oral dose of gatifloxacin 400 mg, blood and urine samples were collected at specified times or intervals over 48 hours to determine drug concentrations.Measurements and Main Results. All 16 subjects (7 with grade B and 1 with grade C hepatic impairment, 8 with normal hepatic function) completed the study. Peak plasma concentration (Cmax) and area under the plasma concentration‐time curve (AUC0–∞) for gatifloxacin were 32% and 22% higher, respectively, in subjects with hepatic impairment. Except for Cmax, the ratio of means for AUC satisfied the specified criterion (0.67–1.50) for lack of effect. There were no statistically significant differences in any other pharmacokinetic values except apparent oral clearance (ClT/F). All treatment‐emergent adverse events were mild or moderate in intensity and resolved before subjects were discharged from the study.Conclusion. Modest increases in Cmax and AUC0–∞ are not anticipated to have a negative effect on the outcome of therapy in hepatically impaired subjects, nor are they anticipated to result in adverse drug reactions. Patients with moderate to severe (Child‐Pugh grade B or C) hepatic dysfunction do not require gatifloxacin dose adjustments. In addition, the similarity in half‐life (t1/2) for the groups (8.9 hrs for hepatically impaired subjects, 9.3 hrs for controls) suggests that no difference would be anticipated in the extent of drug accumulation after multiple doses. The overall safety and tolerability of a single oral dose of gatifloxacin 400 mg were excellent in both healthy subjects and those with hepatic impairment.
The Risk of Gastrointestinal Bleed, Myocardial Infarction, and Newly Diagnosed Hypertension in Users of Meloxicam, Diclofenac, Naproxen, and Piroxicam
Authors: Jick Susan S. 
Published: June 2004

Study Objective. To obtain formally quantified data on the relation of meloxicam to newly diagnosed gastrointestinal problems, myocardial infarction, or treated hypertension.Design. Nested case‐control study.Setting. United Kingdom‐based General Practice Research Database.Patients. Patients who received prescriptions for meloxicam, diclofenac, naproxen, or piroxicam formed the study population. Cases were people who developed gastrointestinal problems, myocardial infarction, or hypertension.Measurements and Main Results. Relative risk estimates for developing the study outcomes were provided for each study nonsteroidal antiinflammatory drug (NSAID), with diclofenac as the reference drug. In no instance was meloxicam associated with an increased risk for a study outcome.Conclusion. Compared with the other NSAIDs, meloxicam was not materially associated with any study outcomes. This study provides reassurance to those prescribing this newer class of NSAIDs.
Lack of Interaction Between Citalopram and the CYP3A4 Substrate Triazolam
Authors: Nolting Arno , Abramowitz Wattanaporn 
Published: June 2004

Study Objectives. To determine the effect of the selective serotonin reuptake inhibitor citalopram on plasma levels of triazolam, and to determine the effect of a single dose of triazolam on steady‐state levels of citalopram and its major metabolites.Design. Open‐label, multidose study.Setting. Clinical Studies, Ltd., Fort Lauderdale, Florida.Participants. Eighteen healthy male and female volunteers.Interventions. Subjects received triazolam 0.25 mg alone and another 0.25mg dose after 4 weeks of citalopram 20 mg/day for 1 week, followed by 3 weeks of citalopram 40 mg/day.Measurements and Main Results. Pharmacokinetic parameters were determined after single‐dose administration of triazolam alone, after administration of citalopram alone at steady state, and after coadministration of the drugs. The pharmacokinetics of triazolam and its metabolite α‐hydroxytriazolam were unchanged by citalopram coadministration. Triazolam appeared to be absorbed slightly more quickly during coadministration. Citalopram kinetics were unaffected by coadministration.Conclusion. No pharmacokinetic interaction between the drugs was observed, suggesting that triazolam and other cytochrome P450 3A4 substrates can be coadministered safely with citalopram.(Pharmacotherapy 2000; 20(7):750–755)
Comparison of Anticoagulant Effects and Safety of Argatroban and Heparin in Healthy Subjects
Authors: Swan Suzanne K. , St. Peter John V. , Lambrecht Lawrence J. , Hursting Marcie J. 
Published: June 2004

Study Objective. To evaluate and compare the relationship between dosage and coagulation parameters, as well as safety profiles, of ascending bolus and infusion dosages of argatroban versus heparin in three phase I studies.Design. Two randomized, double‐blind studies compared argatroban and heparin, and one open‐label, dose‐escalation study further evaluated argatroban.Setting. University teaching hospital clinical research unit.Patients. Healthy men (aged 22–62 yrs).Intervention. In the first study, 36 subjects received an argatroban 30‐, 60‐, 120‐, or 240‐μg/kg bolus, or a heparin 30‐, 60‐, 120‐, or 240‐U/kg bolus for three subjects, then amended to 15, 30, 60, or 120 U/kg. In the second study, 37 subjects received argatroban 1.25, 2.5, 5, or 10 μg/kg/minute with or without a 250‐μg/kg bolus, or heparin 0.15, 0.20, 0.25, or 0.30 U/kg/minute with or without a 125‐U/kg bolus. In the third study (open‐label), nine subjects received an argatroban 250‐μg/kg bolus plus an infusion of 15, 20, 30, and 40 μg/kg/minute.Measurements and Main Results. When administered as a bolus dose in the first study, argatroban and heparin both produced dose‐related increases in activated clotting time (ACT) and activated partial thromboplastin time (aPTT) within 10 minutes of administration. Dissipation of anticoagulant effect was approximately 4‐fold faster for argatroban than for heparin. When administered by infusion with or without a bolus in the second study, argatroban, but not heparin, produced predictable dose‐related increases in ACT and aPTT that were generally consistent across both effect measures and modes of administration. Effect steady state was attained by five or more subjects per dosing group receiving argatroban (5–9) but typically two or fewer subjects per group receiving heparin (0–7). Furthermore, upon cessation of infusion, anticoagulant effects dissipated faster for argatroban (effect half‐life 18–41 min) than for heparin (effect half‐life 23–134 min). When argatroban was infused without a bolus, peak and effect steady‐state values for ACT and aPTT generally were attained within 1–3 hours. Data from the second and third studies show that for argatroban dosages up to 40 μg/kg/minute, plasma drug concentrations attained at 4 hours of infusion increased linearly with dose, and weight‐adjusted plasma clearance was dose independent. In all studies, argatroban and heparin were well tolerated.Conclusion. Anticoagulation was more predictable with argatroban than with heparin as measured by ACT and aPTT, with comparable safety profiles.
Enoxaparin and Bleeding Complications: A Review in Patients with and without Renal Insufficiency
Authors: Gerlach Anthony T. , Pickworth Kerry K. , Seth Shiv K. , Tanna Saloni B. , Barnes Julie F. 
Published: June 2004

Study Objective. To compare the frequency of bleeding complications from enoxaparin in patients with normal renal function versus patients with renal insufficiency.Design. Retrospective chart review.Setting. University‐based tertiary care center.Patients. One hundred six patients who received two or more doses of enoxaparin.Measurements and Main Results. Total bleeding complications occurred in 22% of patients with normal renal function and 51% with renal insufficiency (p<0.01). Major bleeds were also significantly different, 2% and 30%, respectively (p<0.001). No patients with normal renal function were given fresh‐frozen plasma or packed red blood cells, whereas in those with renal insufficiency, 13% and 32%, respectively, received these products (p<0.01).Conclusion. Enoxaparin may have resulted in increased bleeding complications and use of blood products in patients with renal insufficiency. Prospective studies need to be conducted to define the drug's role and dosage adjustments in these patients.(Pharmacotherapy 2000; 20(7):771–775)
Using Focus Groups to Identify Barriers to Drug Use in Patients with Congestive Heart Failure
Authors: Simpson Scot H. , Farris Karen B. , Johnson Jeffrey A. , Tsuyuki Ross T. 
Published: June 2004

Study Objective.To explore barriers to adherence to drug therapy identified by patients with congestive heart failure (CHF).Setting.University‐associated heart failure clinic and a family practice clinic.Patients.Twenty‐six patients with CHF.Intervention.Four focus group sessions.Measurements and Main Results.Participants were asked to describe how their lives changed as a result of developing CHF and the challenges they face when taking drugs for the condition. In the second half of each session, participants were asked for their opinions regarding various teaching and memory aids for improving adherence with therapy. They recognized the value of these aids and often created their own when health care professionals did not supply them. Transcripts were reviewed and comments grouped to identify patient‐perceived barriers to adherence. The disease placed significant limitations on lifestyle. Furosemide had dramatic effects on daily activities, and some patients altered the dosing schedule to accommodate their plans. Influences on adherence were generalized into five themes: confidence in health care providers; their own knowledge regarding the disease and drugs used to treat it; previous experience with drugs; support from family and friends; and ease of communication with health care professionals.Conclusion.Focus groups are an effective and efficient method to explore patients' opinions of barriers to drug therapy adherence. Such information can have a direct impact on management of patients with CHF. Information gathered in this study will be used to construct a survey to measure barriers to drug adherence and design interventions to improve adherence.