PubMed日本語 - ヒト免疫不全ウィルス(HIV)治療の予想外の薬-薬物相互作用:UGT1A1の誘導とエファビレンツによる胆汁外向き流束輸送体。―QLifePro医療翻訳医療翻訳 QLifePro


Unexpected Drug-Drug Interactions in Human Immunodeficiency Virus (HIV) Therapy: Induction of UGT1A1 and Bile Efflux Transporters by Efavirenz.


Published date


Ann Acad Med Singapore. 2012; 41; 559-62;


Lawrence Su Lee, Paul Pham, Charles Flexner


Yong Loo Lin School of Medicine, National University of Singapore, Singapore.


Introduction: Efavirenz is an inducer of drug metabolism enzymes. We studied the effect of efavirenz and ritonavir-boosted darunavir on serum unconjugated and conjugated bilirubin, as probes for UGT1A1 and bile transporters. Materials and Methods: Healthy volunteers were enrolled in a clinical trial. There were 3 periods: Period 1, 10 days of darunavir 900 mg with ritonavir 100 mg once daily; Period 2, 14 days of efavirenz 600 mg with darunavir/ritonavir once daily; and Period 3, 14 days of efavirenz 600 mg once daily. Serum bilirubin (conjugated and unconjugated) concentrations were obtained at baseline, at the end of each phase and at exit. Results: We recruited 7 males and 5 females. One subject developed grade 3 hepatitis on efavirenz and was excluded. Mean serum unconjugated bilirubin concentrations were 6.09 μmol/L (95% confi dence interval [CI], 4.99 to 7.19) at baseline, 5.82 (95% CI, 4.88 to 6.76) after darunavir/ritonavir, 4.00 (95% CI, 2.92 to 5.08) after darunavir/ritonavir with efavirenz, 3.55 (95% CI, 2.58 to 4.51) after efavirenz alone and 5.27 (95% CI, 3.10 to 7.44) at exit (P <0.01 for the efavirenz phases). Mean serum conjugated bilirubin concentrations were 3.55 μmol/L (95% CI, 2.73 to 4.36) at baseline, 3.73 (95% CI, 2.77 to 4.68) after darunavir/ritonavir, 2.91 (95% CI, 2.04 to 3.78) after darunavir/ritonavir with efavirenz, 2.64 (95% CI, 1.95 to 3.33) after efavirenz alone and 3.55 (95% CI, 2.19 to 4.90) at exit (P <0.05 for the efavirenz phases). Conclusion: Efavirenz decreased unconjugated bilirubin by 42%, suggesting UGT1A1 induction. Efavirenz also decreased conjugated bilirubin by 26%, suggesting induction of bile effl ux transporters. Ritonavir-boosted darunavir had no effect on bilirubin concentrations. These results indicate that efavirenz may reduce concentrations of drugs or endogenous substances metabolized by UGT1A1 or excreted by bile effl ux transporters.


3つの期間があった:1日1回リトナビル100mgを使ったダルナビル900mgの1、10日期間;1日1回ダルナビル/リトナビルを使ったエファビレンツ600mgの2、14日期間;そして、3、14 1日1回エファビレンツ600mgの日Period。
平均血清非結合ビリルビン濃度は、終了時にベースラインの6.09μモル/L(95%のconfi dence間隔[CI]、4.99~7.19)、ダルナビル/リトナビルの後の5.82(95%CI、4.88~6.76)、エファビレンツによるダルナビル/リトナビルの後の4.00(95%CI、2.92~5.08)、エファビレンツ単独の後の3.55(95%CI、2.58~4.51)と5.27(95%CI、3.10~7.44)であった(エファビレンツ相の間のP < 0.01)。
平均血清抱合ビリルビン濃度は、終了時にベースラインの3.55μモル/L(95%CI、2.73~4.36)、ダルナビル/リトナビルの後の3.73(95%CI、2.77~4.68)、エファビレンツによるダルナビル/リトナビルの後の2.91(95%CI、2.04~3.78)、エファビレンツ単独の後の2.64(95%CI、1.95~3.33)と3.55(95%CI、2.19~4.90)であった(エファビレンツ相の間のP < 0.05)。
そして、胆汁effl ux輸送体の誘導を示唆した。
これらの結果は、エファビレンツが薬の濃度またはUGT1A1によって代謝されるか、胆汁effl ux輸送体によって排出される内因性の物質を還元する可能性があることを示す。

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