Genetic Influences on the Pharmacokinetics of Orally and Intravenously Administered Digoxin as Exhibited by Monozygotic Twins

被引：9

作者：

Birkenfeld, A. L. ^{[2
,3
]}

Jordan, J. ^{[4
]}

Hofmann, U. ^{[5
,6
]}

Busjahn, A. ^{[7
]}

Franke, G. ^{[2
,3
]}

Krueger, N. ^{[2
,3
]}

Igel, S. ^{[5
,6
]}

Muerdter, T. ^{[5
,6
]}

Drescher, S. ^{[1
,5
,6
]}

Shi, S. ^{[5
,6
,8
]}

Engeli, S. ^{[4
]}

Schwab, M. ^{[5
,6
,9
]}

Eichelbaum, M. ^{[5
,6
]}

Luft, F. C. ^{[2
,3
]}

Fromm, M. F. ^{[1
]}

机构：

[1] Univ Erlangen Nurnberg, Inst Expt & Clin Pharmacol & Toxicol, Dept Clin Pharmacol & Toxicol, Emil Fischer Ctr, Erlangen, Germany

[2] HELIOS Klin, Franz Volhard Clin, Expt & Clin Res Ctr, Berlin, Germany

[3] Charite, Fac Med, Berlin, Germany

[4] Hannover Med Sch, Inst Clin Pharmacol, D-30623 Hannover, Germany

[5] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany

[6] Univ Tubingen, Tubingen, Germany

[7] HealthTwiSt GmbH, Berlin, Germany

[8] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Pharm, Wuhan 430074, Peoples R China

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

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2009年 / 86卷 / 06期

关键词：

INTESTINAL P-GLYCOPROTEIN; DRUG DISPOSITION; MDR1; POLYMORPHISMS; EXPRESSION; CYP3A; BIOAVAILABILITY; HERITABILITY; TRANSPORTERS; INCREASES;

D O I：

10.1038/clpt.2009.170

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The expression and function of the drug transporter P-glycoprotein are highly variable. Environmental and genetic factors contribute to this variation. We studied the disposition of digoxin, a frequently used probe drug for P-glycoprotein function in humans, in monozygotic (MZ) twins and found that digoxin pharmacokinetics after oral and intravenous administration are highly correlated within MZ twins, supporting the hypothesis of a robust contribution from genetic variance. Our study suggests that studies involving twins could be more widely applied to elucidate pharmacogenetics.

引用

页码：605 / 608

页数：4

共 30 条

[1] STEADY-STATE PLASMA LEVELS OF NORTRIPTYLINE INTWINS - INFLUENCE OF GENETIC FACTORS AND DRUG THERAPY [J].

ALEXANDERSON, B ;

EVANS, DAP ;

SJOQVIST, F .

BMJ-BRITISH MEDICAL JOURNAL, 1969, 4 (5686) :764-+

[2] Effects of ursodeoxycholic acid on P-glycoprotein and cytochrome P450 3A4-dependent pharmacokinetics in humans [J].

Becquemont, Laurent ;

Glaeser, Hartmut ;

Drescher, Siegfried ;

Hitzl, Monika ;

Simon, Nicolas ;

Murdter, Thomas E. ;

Heinkele, Georg ;

Hofmann, Ute ;

Schaefer, Christian ;

Burk, Oliver ;

Verstuyft, Celine ;

Eichelbaum, Michel ;

Fromm, Martin F. .

CLINICAL PHARMACOLOGY & THERAPEUTICS, 2006, 79 (05) :449-460

[3] Gene and protein expression of P-glycoprotein, MRP1, MRP2, and CYP3A4 in the small and large human intestine [J].

Berggren, Sofia ;

Gall, Christine ;

Wollnitz, Nadine ;

Ekelund, Mats ;

Karlbom, Urban ;

Hoogstraate, Janet ;

Schrenk, Dieter ;

Lennernas, Hans .

MOLECULAR PHARMACEUTICS, 2007, 4 (02) :252-257

[4] Predicting drug disposition, absorption/elimination/transporter interplay and the role of food on drug absorption [J].

Custodio, Joseph M. ;

Wu, Chi-Yuan ;

Benet, Leslie Z. .

ADVANCED DRUG DELIVERY REVIEWS, 2008, 60 (06) :717-733

[5] Drug-Drug Interactions Mediated Through P-Glycoprotein: Clinical Relevance and In Vitro-In Vivo Correlation Using Digoxin as a Probe Drug [J].

Fenner, K. S. ;

Troutman, M. D. ;

Kempshall, S. ;

Cook, J. A. ;

Ware, J. A. ;

Smith, D. A. ;

Lee, C. A. .

CLINICAL PHARMACOLOGY & THERAPEUTICS, 2009, 85 (02) :173-181

[6] Effects of a chargrilled meat diet on expression of CYP3A, CYP1A, and P-glycoprotein levels in healthy volunteers [J].

Fontana, RJ ;

Lown, KS ;

Paine, MF ;

Fortlage, L ;

Santella, RM ;

Felton, JS ;

Knize, MG ;

Greenberg, A ;

Watkins, PB .

GASTROENTEROLOGY, 1999, 117 (01) :89-98

[7] Importance of P-glycoprotein at blood-tissue barriers [J].

Fromm, MF .

TRENDS IN PHARMACOLOGICAL SCIENCES, 2004, 25 (08) :423-429

[8] Carbamazepine regulates intestinal P-glycoprotein and multidrug resistance protein MRP2 and influences disposition of talinolol in humans [J].

Giessmann, T ;

May, K ;

Modess, C ;

Wegner, D ;

Hecker, U ;

Zschiesche, M ;

Dazert, P ;

Grube, M ;

Schroeder, E ;

Warzok, R ;

Cascorbi, I ;

Kroemer, HK ;

Siegmund, W .

CLINICAL PHARMACOLOGY & THERAPEUTICS, 2004, 76 (03) :192-200

[9] The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin [J].

Greiner, B ;

Eichelbaum, M ;

Fritz, P ;

Kreichgauer, HP ;

Von Richter, O ;

Zundler, J ;

Kroemer, HK .

JOURNAL OF CLINICAL INVESTIGATION, 1999, 104 (02) :147-153

[10] Effects of pregnancy on CYP3A and P-glycoprotein activities as measured by disposition of midazolam and digoxin: A University of Washington specialized center of research study [J].

Hebert, M. F. ;

Easterling, T. R. ;

Kirby, B. ;

Carr, D. B. ;

Buchanan, M. L. ;

Rutherford, T. ;

Thummel, K. E. ;

Fishbein, D. P. ;

Unadkat, J. D. .

CLINICAL PHARMACOLOGY & THERAPEUTICS, 2008, 84 (02) :248-253

← 1 2 3 →