BACKGROUND E-52862 is a Sigma-1 receptor antagonist (S1RA) currently under investigation as a potential analgesic medicine. We successfully applied a concentration-effect model retrospectively to a four-way crossover Phase I single ascending dose study and utilized the QTc shortening effects of a meal to demonstrate assay sensitivity by establishing the time course effects from baseline in all ...

Twelve healthy volunteers were enrolled in an open-label, randomized, crossover study. Subjects received single doses of theophylline (5 mg/kg) with and without multiple-dose terbinafine, and 11 blood samples were collected over 24 h. The study phases were separated by a 4-week washout period. Theophylline serum data were modeled via noncompartmental analysis. When the control phase (i.e., no t...

Lopinavir is a new specific and potent HIV-1 protease inhibitor. A simple and rapid Reverse Phase High-Performance Liquid Chromatographic method using UV detection was developed and validated for the analysis of lopinavir in rat plasma under isocratic conditions. The method involves a single step protein precipitation technique. The detector response was linear over the concentration range of 2...

We provide some details of the implementation of optimal design algorithm in the PkStaMp library which is intended for constructing optimal sampling schemes for pharmacokinetic (PK) and pharmacodynamic (PD) studies. We discuss different types of approximation of individual Fisher information matrix and describe a user-defined option of the library.

BACKGROUND Exploratory preclinical, as well as clinical trials, may involve a small number of patients, making it difficult to calculate and analyze the pharmacokinetic (PK) parameters, especially if the PK parameters show very high inter-individual variability (IIV). In this study, the performance of a classical first-order conditional estimation with interaction (FOCE-I) and expectation maxim...

Pharmacokinetic parameters of cefaclor were studied in eight patients after an oral dose of 250 mg. Serum samples were obtained before and on 19 occasions after oral administration. Cefaclor serum concentrations were determined by a new high-performance liquid chromatographic technique.

We hypothesize that a representation of drug-drug interactions (DDIs) based on physiologic, pharmacokinetic (PK) and pharmacodynamic (PD) mechanisms will provide more accurate and useful information to clinicians than current approaches that simply tabulate and index pairwise interactions of drugs. This paper explores the strengths, weaknesses, and difficulties of modeling drug mechanisms and r...

The literature on the pharmacokinetics of vancomycin in patients undergoing extracorporeal membrane oxygenation (ECMO) therapy is sparse. A population pharmacokinetic (PK) model for vancomycin in ECMO patients was developed using a nonlinear mixed effects modeling on the concentration-time profiles of 14 ECMO patients who received intravenous vancomycin. Model selection was based on log-likelih...

In the pharmacokinetic (PK) study under a 2x2 crossover design that involves both the test and reference drugs, we propose a mixed-effects model for the drug concentration-time profiles obtained from subjects who receive different drugs at different periods. In the proposed model, the drug concentrations repeatedly measured from the same subject at different time points are distributed accordin...

4. There are universally applicable formulae for systemically acting (including antimicrobial) drugs which: (a) define the relationship between the 3 pivotal pharmacokinetic (PK) parameters, clearance, volume of distribution and elimination half-life; (b) define drug action (pharmacodynamics, PD) quantitatively through the sigmoidal Emax equation, linking concentration to effect; (c) predict a ...