PubMed Health⌕ Search

Biomedical subjects

J Koup

Publications and source records attributed to J Koup.

6 recordsLinked to original sources
PubMed2001

Population pharmacokinetics of clinafloxacin in healthy volunteers and patients with infections: experience with heterogeneous pharmacokinetic data.

OBJECTIVE: Clinafloxacin is a new fluoroquinolone antibacterial with inhibitory activity against aerobic, anaerobic and atypical bacterial pathogens. The objectives of this study are to evaluate the pharmacokinetics of clinafloxacin in healthy volunteers and patients with infections and to describe our experience with mixed-effects modelling using heterogeneous pharmacokinetic data. DESIGN AND SETTING: Retrospective analysis of data from phase I to III trials. PATIENTS AND PARTICIPANTS: 204 healthy volunteers and 221 patients with infections. METHODS: Nonlinear mixed-effects modelling (MEM) was used to evaluate 3437 clinafloxacin plasma concentrations collected in 15 phase I to III trials. Models were developed separately for the healthy volunteers and patients, and then for the combined study population. RESULTS: The phase I data were best described with a 2-compartment linear model with first-order absorption. The absorption lag-time and absorption rate constant were 0.24h and 1.17h(-1), respectively. The volumes of distribution were found to be nonlinear functions of body surface area. Estimated creatinine clearance was the most important covariate for systemic clearance (CL). Interoccasion variability (IOV) in CL was observed in the patients in the phase II trial. In the combined study population, the variability in CL was best described by a model including IOV and distinct variabilities for healthy volunteers and patients. CONCLUSION: MEM was useful for evaluating data collected during different phases of drug development for this new fluoroquinolone agent.

Administration, Oral↗
PubMed1993

TopFit: a PC-based pharmacokinetic/pharmacodynamic data analysis program.

The program TopFit was developed and validated within the European pharmaceutical industry. It provides both pharmacokinetic data analysis support for international regulatory submissions of new drugs, and sophisticated techniques for model-based kinetic/dynamic evaluation during drug development. TopFit features are: (1) non-compartmental methods; (2) standard compartment models assembled from input and disposition modules; (3) a potentially unlimited number of linear user-defined models that accommodate metabolites, effects, and absorption profiles; (4) a library of 24 non-linear models. No user programming is required. A well-defined file structure allows ready exchange of data with other programs such as SAS. TopFit version 2.0 is now commercially available, with comprehensive documentation, in the form of an MS-DOS application for the PC.

Data Interpretation, Statistical↗
PubMed1981

Evaluation of two methods for estimating theophylline clearance prior to achieving steady state.

The Koup et al. and Chiou et al. clearance estimation methods were evaluated n 19 chronic obstructive pulmonary disease (COPD)/asthmatic patients who were receiving aminophylline by continuous infusion. Estimated theophylline clearance (Clest) was determined using two serum concentrations obtained during the first few hours of therapy (1-16 hr) prior to achievement of steady state. Actual theophylline clearance (Clact) was determined after steady state conditions had been achieved (defined as 4-5 half-lives at the same infusion rate). The correlation between Clact and Clest was highly significant for both the Koup et al. and Chiou et al. methods, r = 0.865, p less than 0.001, and r = 0.858, p less than 0.001, respectively. The clearance estimation methods were compared with the Food and Drug Administration (FDA) dosage guidelines and shown to be clearly superior in predicting therapeutic steady state theophylline concentrations.

Aminophylline↗
PubMed1981

Effect of exchange transfusion on serum gentamicin concentrations.

To determine whether an exchange transfusion increases the rate of elimination of gentamicin, we measured drug (and bilirubin) concentration either before and during, or during and after a standard two-volume exchange procedure in 7 newborns. In an additional 5 infants, serum was obtained only on initiation and conclusion of the procedure. The mean decrement in serum gentamicin concentration with the procedure was 2.2 micrograms/ml; this was 25.7% of the original mean concentration. The mean elimination rate constant during the procedure was 0.342 h-1, a value significantly greater (p = 0.013) than the mean rate before or after the procedure, 0.104 h-1. We conclude that the exchange transfusion procedure significantly increases the rate of gentamicin elimination. The decrement produced by the procedure may result in subtherapeutic concentrations, if the initial values are marginally efficacious.

Analysis of Variance↗