Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2487885 | Journal of Pharmaceutical Sciences | 2006 | 9 Pages |
Abstract
Present study aims to improve efficiency and capacity of in vivo rat pharmacokinetic studies for rapid assessment of systemic exposure (AUC and Cmax) of new chemical entities. Plasma concentration-time profiles in rats from structurally diverse compounds were extracted from the Pfizer database. AUC0-8 was calculated with 7 data points or a reduced subset of 3 data points. AUC values determined with 7 data points were compared to subset AUC values. A â¤Â 30% difference in values for 90% of cases was acceptance criteria. In parallel, samples were analyzed individually and pooled at each time point across compounds. For 96% of cases, AUC values estimated using 1, 4, and 8 h were comparable to AUC values obtained from 7 data points suggesting 1, 4, and 8 h sampling should be sufficient to estimate AUC. For Cmax, the difference between 1, 4, and 8 h data-point analysis versus 7 data-point analysis is less than 30% for 72% of cases. Concentrations from individual versus pooled sample analysis were found to be equivalent. A rapid rat PK screening paradigm was created by the combination of 1, 4, and 8 h sampling and pooled sample analysis, which improves throughput and cycle time of in vivo PK studies.
Keywords
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Hyo-Kyung Han, Nalini Sadagopan, Gregory A. Reichard, Udeni Yapa, Tong Zhu, Andrea Hubbel, Kjell Johnson, Joanne Brodfuehrer,