This approach is the standard one when one uses parametric compartmental pharmacokinetic (PK) models. The usual parameter values are either the mean or median as the descriptor of the central tendency, and the standard deviation (SD) as the measure of dispersion. The usual distribution is the common Gaussian bell-shaped curve. Usually the mean is the central value used, and the distribution is ...

Monoclonal antibodies (mAbs) have developed in the last two decades into the backbone of pharmacotherapeutic interventions in a variety of indications, with currently more than 40 mAbs approved by the US Food and Drug Administration, and several dozens more in clinical development. This tutorial will review major drug disposition processes relevant for mAbs, and will highlight product-specific ...

BACKGROUND Available alfentanil pharmacokinetic (PK) sets for target-controlled infusion (TCI) were derived from populations with normal BMI. The performance and accuracy of the models devised by Maitre and colleagues and Scott and colleagues were evaluated in a population including morbidly obese patients. METHODS Alfentanil TCI using Maitre and colleagues' model was administered to 10 obese...

This article provides a fully bayesian approach for modeling of single-dose and complete pharmacokinetic data in a population pharmacokinetic (PK) model. To overcome the impact of outliers and the difficulty of computation, a generalized linear model is chosen with the hypothesis that the errors follow a multivariate Student t distribution which is a heavy-tailed distribution. The aim of this s...

AIM We compared the pharmacokinetic (PK) profiles of co-crystal of tramadol-celecoxib (CTC) vs. each reference product (alone and in open combination) after single (first dose) and multiple dosing. METHODS Healthy adults aged 18-50 years received, under fasted conditions, 15 twice-daily doses of the following treatments (separated by ≥14-day washout): 200 mg immediate-release (IR) CTC (equiva...

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 ...

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...

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...