We show through a simulation study how the joint analysis of data from phase I and phase II studies enhances the power of pharmacogenetic tests in pharmacokinetic (PK) studies. PK profiles were simulated under different designs along with 176 genetic markers. The null scenarios assumed no genetic effect, while under the alternative scenarios, drug clearance was associated with six genetic marke...

The purpose of this clinical study was to investigate the influence of concomitant drug therapy with ciprofloxacin and rifampin on the individual pharmacokinetic profile of each agent in elderly patients. Twelve nursing home patients (age, 74 +/- 7 years), colonized with methicillin-resistant Staphylococcus aureus, were randomized to receive 14-day therapy with oral ciprofloxacin (750 mg every ...

Validating an exposure pathway model is difficult because the biomarker, which is often used to evaluate the model prediction, is an integrated measure for exposures from all the exposure routes and pathways. The purpose of this article is to demonstrate a method to use pharmacokinetic (PK) modeling and computer simulation to guide the design of field studies to validate pathway models. The chi...

BACKGROUND We investigated how one pharmacokinetic (PK) model differed in prediction of plasma (C(p)) and effect-site concentration (C(eff)) using a reproducing simulation of target-controlled infusion (TCI) with another PK model of propofol. METHODS Sixty female patients were randomly assigned to TCI using Marsh PK (Group M) and TCI using Schnider PK (Group S) targeting 6.0 µg/ml of C(p) of ...

Our laboratory is engaged in an ongoing analysis of a 103-compound data set containing reliable intravenous pharmacokinetic parameters in the rat, dog, monkey, and human, and we have previously reported our findings regarding extrapolation of clearance. In this article, we report on our findings regarding volume of distribution and mean residence time. Various allometric and nonallometric metho...

The pharmacokinetics of ceftriaxone were investigated in six healthy mainland Chinese adults (four males and two females). A single 1.0-g dose was administered intravenously or intramuscularly in a two-way crossover design. Plasma and saliva samples were collected on 11 occasions between 0 and 36 h after dosing. Ceftriaxone was not detected in any saliva samples. The mean volume of distribution...

Predictive performance of physiologically based pharmacokinetic (PBPK) and population pharmacokinetic (PopPK) models of drugs predominantly eliminated through kidney in the pediatric population was evaluated. After optimization using adult clinical data, the verified PBPK models can predict 33 of 34 drug clearance within twofold of the observed values in children 1 month and older. More specifi...

Identification of the human genetic health hazard from exposure to chemicals of a diverse nature is of significant importance from a public health standpoint. A wide variety of organisms ranging from phage to human cells in culture may be used as tester strains to identify the mutagenic capability of a chemical. While these systems do supply genetically useful information, their major limitatio...

Sevoflurane has been available for clinical practice for about 20 years. Nowadays, its pharmacodynamic and pharmacokinetic properties together with its absence of major adverse side effects on the different organ systems have made this drug accepted worldwide as a safe and reliable anesthetic agent for clinical practice in various settings.