The NTCP-inhibitor Myrcludex B: Effects on Bile Acid Disposition and Tenofovir Pharmacokinetics

被引：71

作者：

Blank, A. ^{[1
,2
]}

Eidam, A. ^{[1
,2
]}

Haag, M. ^{[3
,4
]}

Hohmann, N. ^{[1
,2
]}

Burhenne, J. ^{[1
,2
]}

Schwab, M. ^{[3
,4
,5
,6
]}

van de Graaf, S. F. J. ^{[7
,8
]}

Meyer, M. R. ^{[1
,9
]}

Maurer, H. H. ^{[9
]}

Meier, K. ^{[1
,2
]}

Weiss, J. ^{[1
,2
]}

Bruckner, T. ^{[10
]}

Alexandrov, A. ^{[11
]}

Urban, S. ^{[2
,12
]}

Mikus, G. ^{[1
,2
]}

Haefeli, W. E. ^{[1
,2
]}

机构：

[1] Heidelberg Univ Hosp, Dept Clin Pharmacol & Pharmacoepidemiol, Heidelberg, Germany

[2] German Ctr Infect Res DZIF, Heidelberg Partner Site, Heidelberg, Germany

[3] Univ Tubingen, Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany

[4] German Ctr Infect Res DZIF, Tubingen Partner Site, Tubingen, Germany

[5] Univ Hosp Tubingen, Dept Clin Pharmacol, Tubingen, Germany

[6] Univ Tubingen, Dept Pharm & Biochem, Tubingen, Germany

[7] Acad Med Ctr, Tytgat Inst Liver & Intestinal Res, Amsterdam, Netherlands

[8] Acad Med Ctr, Dept Gastroenterol & Hepatol, Amsterdam, Netherlands

[9] Saarland Univ, Expt & Clin Toxicol, Homburg, Germany

[10] Heidelberg Univ Hosp, Inst Med Biostat & Med Informat, Heidelberg, Germany

[11] Myr GmbH, Bad Homburg, Germany

[12] Heidelberg Univ Hosp, Dept Infect Dis, Mol Virol, Heidelberg, Germany

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2018年 / 103卷 / 02期

关键词：

HEPATITIS-B; SUBSTRATE MIDAZOLAM; DISOPROXIL FUMARATE; VIRUS; ENTRY; POLYPEPTIDE; TRANSPORTERS; RECEPTORS; ENZYMES;

D O I：

10.1002/cpt.744

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Myrcludex B acts as a hepatitis B and D virus entry inhibitor blocking the sodium taurocholate cotransporting polypeptide (SLC10A1). We investigated the effects of myrcludex B on plasma bile acid disposition, tenofovir pharmacokinetics, and perpetrator characteristics on cytochrome P450 (CYP) 3A. Twelve healthy volunteers received 300 mg tenofovir disoproxil fumarate orally and 10 mg subcutaneous myrcludex B. Myrcludex B increased total plasma bile acid exposure 19.2-fold without signs of cholestasis. The rise in conjugated bile acids was up to 124-fold (taurocholic acid). Coadministration of tenofovir with myrcludex B revealed no relevant changes in tenofovir pharmacokinetics. CYP3A activity slightly but significantly decreased by 29% during combination therapy. Myrcludex B caused an asymptomatic but distinct rise in plasma bile acid concentrations and had no relevant impact on tenofovir pharmacokinetics. Changes in CYP3A activity might be due to alterations in bile acid signaling. Long-term effects of elevated bile acids will require critical evaluation.

引用

页码：341 / 348

页数：8

共 41 条

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