Elizabeth Weise, a USA Today journalist, posted a story titled “Journals: USA, others need to re-tool their science programs” on April 22, 2011 (link). The premise of the article is that the journal Nature is reporting that there are not enough academic positions available for the number of PhD graduates, and that non-academic industries are … Continued
We describe a framework for estimating the human dose at which a chemical significantly alters a biological pathway in vivo, making use of in vitro assay data and an in vitro-derived pharmacokinetic model, coupled with estimates of population variability and uncertainty. The quantity we calculate, the biological pathway altering dose (BPAD), is analogous to current … Continued
TBR-652 is a novel CCR5 antagonist with potent in vitro anti-HIV activity. The objective of this study was to determine the pharmacokinetics (PK) and pharmacodynamics (PD) of TBR-652 in HIV-1-infected, antiretroviral treatment-experienced, CCR5 antagonist-naive patients. A double-blind, placebo-controlled, randomized, dose-escalating study of TBR-652 monotherapy given once daily orally for 10 days was performed followed by … Continued
One of the key things to do during the transition from preclinical development studies to clinical development studies is to set the target for your drug assay limit of quantification (LOQ). I will outline a few considerations on that topic. Here are my main assumptions: You are working with a drug that is intended for … Continued
BLQ values are like those pimples we used to get as teenagers. They often show up at the worst time and they always seem to be in the wrong place. (Is their really a “right” place for a pimple!?) Then what do you do with the pimple? Rub some alcohol on it, put other medication, … Continued
When performing non-compartmental analysis, the area under the concentration-time curve (AUC) is calculated to determine the total drug exposure over a period of time. Together with Cmax, these two parameters are often used to define the systemic exposure of a drug for comparison purposes. For example, in bioequivalence trials, the entire statistical analysis is based … Continued
This study aimed to test whether a pharmacokinetic simulation model could extrapolate nonclinical drug data to predict human efavirenz exposure after single and continuous dosing as well as the effects of concomitant rifampicin and further to evaluate the weight-based dosage recommendations used to counteract the rifampicin–efavirenz interaction. Efavirenz pharmacokinetics were simulated using a physiologically based … Continued
