Abstract：
:Present study aims to improve efficiency and capacity of in vivo rat pharmacokinetic studies for rapid assessment of systemic exposure (AUC and C(max)) of new chemical entities. Plasma concentration-time profiles in rats from structurally diverse compounds were extracted from the Pfizer database. AUC(0-8) 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 < or = 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 C(max), 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.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Han HK,Sadagopan N,Reichard GA,Yapa U,Zhu T,Hubbel A,Johnson K,Brodfuehrer Jdoi
10.1002/jps.20642subject
Has Abstractpub_date
2006-08-01 00:00:00pages
1684-92issue
8eissn
0022-3549issn
1520-6017pii
S0022-3549(16)32078-0journal_volume
95pub_type
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