Nonparametric expectation maximisation (NPEM) population pharmacokinetic analysis of caffeine disposition from sparse data in adult caucasians: systemic caffeine clearance as a biomarker for cytochrome P450 1A2 activity.

Objective: To explore the ability of the nonparametric expectation maximisation (NPEM) method of population pharmacokinetic modelling to deal with sparse data in estimating systemic caffeine clearance for monitoring and evaluation of cytochrome P450 (CYP) 1A2 activity.

Design And Participants: Nonblind, single-dose clinical investigation in 34 non-related adult Bulgarian Caucasians (18 women and 16 men, aged between 18 and 62 years) with normal and reduced renal function.

Methods: Each participant received oral caffeine 3 mg/kg.

Pharmacokinetic variability of nimodipine disposition after single and multiple oral dosing to hypertensive renal failure patients: parametric and nonparametric population analysis.

Objectives: To explore the contribution of renal failure to nimodipine overall pharmacokinetic variability after single and multiple oral dosing and to develop a population pharmacokinetic model by means of the nonparametric expectation maximization (NPEM2) algorithm based on sampled individual drug concentrations close to the estimated patients' C(SS)avs (NPEM2-C(SS)av).

Patients, Materials And Methods: 24 hypertensive patients with normal and reduced renal function, without clinical and laboratory data for hepatic dysfunction, were enrolled in the study and their nimodipine plasma levels were analyzed by means of a parametric and nonparametric population pharmacokinetic modeling using a maximum a posteriori Bayesian (MAPB) estimator in an iterative two-stage Bayesian population modeling program and NPEM2-algorithm.

Results: Comparison of parameter dispersion revealed higher variability of nimodipine disposition after the first dose than at steady-state except for apparent volume of distribution at steady-state, V(SS)/F, whose variability increased from 98% to 223%.

Population pharmacokinetics of ciprofloxacin in patients with liver impairments analyzed by NPEM2 algorithm--a retrospective study.

In order to develop a population pharmacokinetic model for ciprofloxacin after single oral dosing in patients with liver impairments, a retrospective population analysis of already published data was undertaken. The purpose of the study was to compare the population model parameter estimates for ciprofloxacin obtained with the non-parametric expectation maximization (NPEM2) algorithm based on a full data set (NPEM2-FULL) with those based on a set of 3 randomly chosen time/concentrations data (NPEM2-3RPs). Parameter values generated by the standard two-stage (STS) approach using traditional data-rich situation were used as a "gold standard" for comparative purposes.