AbbVie Inc., North Chicago, Illinois, USA.
Clin Pharmacol Drug Dev. 2021 Nov;10(11):1335-1344. doi: 10.1002/cpdd.957. Epub 2021 Jun 9.
This phase 1, 2-part, 2-period, open-label, drug-drug interaction study evaluated the potential for pharmacokinetic interactions between upadacitinib and rosuvastatin, an organic anion transporting polypeptide (OATP) 1B1 and breast cancer resistance protein substrate, or atorvastatin, a cytochrome P450 3A, OATP1B1, and OATP1B3 substrate, in 36 healthy volunteers. During period 1, a single dose of rosuvastatin (5 mg; part 1) or atorvastatin (10 mg; part 2) was administered on day 1, followed by a washout period of 5 days. During period 2, once-daily doses of upadacitinib extended-release (30 mg) were administered on days 1 to 10, and a single dose of rosuvastatin (5 mg; part 1) or atorvastatin (10 mg; part 2) was administered 1 hour after the upadacitinib dose on day 7. Serial blood samples were collected for assays of drug concentrations. In Part 1, rosuvastatin maximum observed plasma concentration (C ) and area under the plasma concentration-time curve from time 0 to infinity (AUC ) were 23% and 33% lower, respectively, when administered with upadacitinib relative to when administered alone. In part 2, atorvastatin C and AUC was 11% and 23% lower, respectively, when administered with upadacitinib relative to when administered alone. The C and AUC of the active metabolite ortho-hydroxyatorvastatin remained unchanged. Administration of a single 5-mg dose of rosuvastatin or a single 10-mg dose of atorvastatin had no relevant effect on upadacitinib C or area under the plasma concentration-time curve. These results demonstrated that upadacitinib has no clinically relevant effect on the pharmacokinetics of rosuvastatin and atorvastatin or on substrates transported by OATP1B or breast cancer resistance protein.
这项 1 期、2 部分、2 周期、开放性、药物相互作用研究评估了 upadacitinib 与 rosuvastatin（一种有机阴离子转运多肽 [OATP] 1B1 和乳腺癌耐药蛋白底物）或 atorvastatin（一种细胞色素 P450 3A、OATP1B1 和 OATP1B3 底物）之间潜在的药代动力学相互作用，共有 36 名健康志愿者参与。在第 1 期间，第 1 部分中单次给予 rosuvastatin（5mg）或第 2 部分中单次给予 atorvastatin（10mg），然后进行 5 天的洗脱期。在第 2 期间，每天给予一次 upadacitinib 缓释制剂（30mg），并在第 7 天 upadacitinib 剂量后 1 小时给予单次 rosuvastatin（5mg；第 1 部分）或 atorvastatin（10mg；第 2 部分）。连续采集血样进行药物浓度检测。在第 1 部分中，与单独给予 rosuvastatin 相比，与 upadacitinib 同时给予 rosuvastatin 时其最大观测血浆浓度（C ）和从 0 到无穷大的血浆浓度-时间曲线下面积（AUC ）分别降低了 23%和 33%。在第 2 部分中，与单独给予 atorvastatin 相比，与 upadacitinib 同时给予 atorvastatin 时其 C 和 AUC 分别降低了 11%和 23%。活性代谢物 ortho-hydroxyatorvastatin 的 C 和 AUC 保持不变。单次给予 5mg rosuvastatin 或单次给予 10mg atorvastatin 对 upadacitinib 的 C 或血浆浓度-时间曲线下面积无相关影响。这些结果表明，upadacitinib 对 rosuvastatin 和 atorvastatin 的药代动力学或对 OATP1B 或乳腺癌耐药蛋白转运的底物无临床相关影响。
