Population pharmacokinetics of tipifarnib in healthy subjects and adult cancer patients.

Aims: To characterize the population pharmacokinetics of tipifarnib.

Methods: A total of 1083 subjects treated orally with a solution, capsule or tablet formulations of tipifarnib, given as a single dose or as multiple twice-daily doses (range 25-1300 mg) were combined with data from 1, 2 and 24 h intravenous infusions. A total of 3445 concentrations in the index data set were fitted by an open three-compartment linear disposition model with sequential zero-order input into the depot compartment, followed by a first-order absorption process, and lag time, using NONMEM V.

Population pharmacokinetic analysis of pegylated human erythropoietin in rats.

The purpose of this study was to model the pharmacokinetics of the pegylated human erythropoietin (PEG-EPO) after single-dose administration in rats, and to evaluate the influence of weight, sex, and pregnancy status on the pharmacokinetic parameters. A total of 436 serum concentrations from 193 Sprague-Dawley rats were obtained from four pharmacokinetic/toxicokinetic studies, in which a single dose of PEG-EPO was administered by the intravenous (i.v.

Population pharmacokinetics of enterally administered cisapride in young infants with gastro-oesophageal reflux disease.

Aims: To investigate the pharmacokinetics of enterally administered cisapride suspension in young infants being treated for gastro-oesophageal reflux disease.

Methods: Plasma cisapride concentrations in 49 subjects (weight: 825-5010 g; n=108 samples, median two per patient; concentration: 14.8-170 ng ml-1 ) were fitted to a one-compartment model with first-order absorption and elimination in the NONMEM program using a logarithmic transformation of the observed and predicted concentrations.

Population analysis of the non linear red blood cell partitioning and the concentration-effect relationship of draflazine following various infusion rates.

Aims: To investigate the impact of the specific red blood cell binding on the pharmacokinetics and pharmacodynamics of the nucleoside transport inhibitor draflazine after i.v. administration at various infusion rates.

A model with separate hepato-portal compartment ("first-pass" model): fitting to plasma concentration-time profiles in humans.

Purpose: To demonstrate the value of "first-pass" pharmacokinetic models (FPMs) in which the hepato-portal (HP) system is kinetically separated from the central compartment in fitting pharmacokinetic data obtained after intravenous (IV) and oral administration.

Methods: Plasma concentration-time profiles of an investigational drug obtained in six healthy subjects each received 4 mg as an intravenous (IV) bolus dose and 10 mg as an oral solution served as a real data example. The common three- and four-compartment models with the first-order absorption and lag time (3CM and 4CM, respectively) in which HP system is assumed to be part of the central compartment were used as alternative models.