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 ...

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...

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.

Pharmacokinetic (PK) parameters of marbofloxacin (MRFX) in Korean cattle, Hanwoo, were determined following its intravenous (i.v.) or intramuscular (i.m.) administration at a dose of 2 mg/kg. Area under the curve (AUC0-24 hr), half-life (t1/2) and total body clearance (CLB) of i.v. MRFX were 6.87 hr∙µg/ml, 2.44 hr and 0.29 l/kg∙hr, respectively, and the corresponding values for i.m. administrat...

In this paper, the problem of interest is efficient estimation of log-normal means. Several existing estimators are reviewed first, including the sample mean, the maximum likelihood estimator, the uniformly minimum variance unbiased estimator and a conditional minimal mean squared error estimator. A new estimator is then proposed, and we show that it improves over the existing estimators in ter...

To interpret pharmacokinetic (PK) data of biotherapeutics, it is critical to understand which drug species is being measured by the PK assay. For therapeutic antibodies, it is generally accepted that "free" circulating antibodies are the pharmacologically active form needed to determine the PK/pharmacodynamic (PD) relationship, safety margin calculations, and dose projections from animals to hu...

CONTEXT In a previous work, we have shown that penalized regression approaches can allow many genetic variants to be incorporated into sophisticated pharmacokinetic (PK) models in a way that is both computationally and statistically efficient. The phenotypes were the individual model parameter estimates, obtained a posteriori of the model fit and known to be sensitive to the study design. OBJ...

Hemoglobin (Hb) is an ideal material for use in the development of an oxygen carrier in view of its innate biological properties. However, the vascular retention of free Hb is too short to permit a full therapeutic effect because Hb is rapidly cleared from the kidney via glomerular filtration or from the liver via the haptogloblin-CD 163 pathway when free Hb is administered in the blood circula...