Genotype, Ethnicity, and Drug-Drug Interaction Modeling as Means of Verifying Transporter Biomarker PBPK Model: The Coproporphyrin-I Story.

• Tác giả: Aleksandra Galetin, Daniel Scotcher, Shawn Pei Feng Tan, Yuki Ujihira
• Ngôn ngữ: eng
• Ký hiệu phân loại: 616.8918 Diseases of nervous system and mental disorders
• Thông tin xuất bản: United States : CPT: pharmacometrics & systems pharmacology , 2025
• Bộ sưu tập: NCBI
• ID: 686644

Tóm tắt

 Coproporphyrin-I (CP-I) is a selective endogenous biomarker of organic anion-transporting polypeptide (OATP)1B. Multiple CP-I PBPK models with differing input parameters have been reported so far. This study proposed a harmonized CP-I PBPK model and evaluated its ability to predict the effect of ethnicity, SLCO1B1 genotype c.521T>
 C, and sex on CP-I baseline and CP-I-drug interactions using the largest clinical dataset to date. The CP-I PBPK model successfully predicted CP-I plasma baseline from 731 subjects, with 97% of predictions within 1.5-fold of the observed data. Prediction of weak, moderate, and strong OATP1B-mediated interactions with probenecid, low-dose cyclosporine, and rifampicin, respectively, was evaluated with 21 datasets. Overall, >
  76% of CP-I C