- |||||||||| Rovatitan (rosuvastatin/valsartan) / LG Chem, Livalo (pitavastatin) / Kowa, Eli Lilly
PK/PD data, Journal: Physiologically-based pharmacokinetic model-based translation of OATP1B-mediated drug-drug interactions from coproporphyrin I to probe drugs. (Pubmed Central) - Jun 22, 2022
Here, we report a physiologically-based pharmacokinetic (PBPK) model analysis for clinical DDI data generated in heathy subjects who received oral doses of cyclosporin A (CysA; 20 and 75 mg) as an OATP1B inhibitor, and the probe drugs (pitavastatin, rosuvastatin, and valsartan)...Based on the accepted 498 parameter sets, the range of CL and K was narrowed, with coefficients of variation (CVs) of 9.3% and 11.1%, respectively, indicating that these parameters were practically identifiable. These results suggest that PBPK model analysis of CP-I is a promising translational approach to predict OATP1B-mediated DDIs in drug development.
- |||||||||| cyclosporin A microemulsion / Generic mfg.
Journal: Effect of cyclosporin A and impact of dose staggering on OATP1B1/1B3 endogenous substrates and drug probes for assessing clinical drug interactions. (Pubmed Central) - May 22, 2022
Non-linear regression analysis of AUCR of pitavastatin and CP-I against CysA C yielded K (109 ± 35 and 176±42 nM, respectively), similar to the K estimated by our physiologically based pharmacokinetic model analysis described previously (107 nM). The endogenous OATP1B1/1B3 biomarkers, particularly C R and AUCR of CP-I, corroborates OATP1B1/1B3 inhibition and yields valuable information that improve accurate DDI predictions in drug development, and enhance our understanding of interindividual variability in the magnitude of DDI.
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