Effects of multidose simvastatin co-administration on pharmacokinetic profile of apatinib in rats by UPLC-MS/MS.

Effects of multidose simvastatin co-administration on pharmacokinetic profile of apatinib in rats by UPLC-MS/MS. Xenobiotica. 2020 Mar 09;:1-21 Authors: Gao J, Ren H, Feng Z, Chen S, Liang Y, Liu W, Zhou Q, Wang M Abstract Apatinib, a small molecule anti-angiogenic tyrosine kinase inhibitor (TKI), is used extensively to treat advanced gastric cancer and simvastatin (SV) is often co-prescribed to treat cardiovascular disease in cancer patients. As both apatinib and SV are metabolized primarily by CYP3A4, they are likely to interact. Therefore, the potential effect of SV co-administration on pharmacokinetics of apatinib in Sprague-Dawley male rats is demonstrated for the first time.Sixteen rats were randomly divided into two groups (n = 8), group B (2 mg/kg SV orally co-administrated for 7 days) and the corresponding control group (group A). Apatinib concentrations of rat plasma samples were detected by UPLC-MS/MS. Pharmacokinetic parameters were calculated using non compartmental methods.Co-administration of SV for 7 days significantly increased AUC(0-t), AUC(0-∞) and Cmax of apatinib by 2.4-fold, 2.4-fold and 2.7-fold, while decreasing Vz/F and CLz/F by 81.7% and 73.9%.These findings suggest that concomitant administration of SV with 7 days may have inhibited the metabolism of apatinib in rats. PMID: 32150479 [PubMed - as supplied by publisher]
Source: Xenobiotica - Category: Research Authors: Tags: Xenobiotica Source Type: research