TY - JOUR
AU - Otsubo, Kenji
AB - Role of human MDR1 gene polymorphism in bioavailability and interaction of digoxin, a substrate of P-glycoprotein Objective: Our objective was to quantitate the contribution of the genetic polymorphism of the human MDR1 gene to the bioavailability and interaction profiles of digoxin, a substrate of P-glycoprotein. Methods: The pharmacokinetics of digoxin was studied in 15 healthy volunteers, who were divided into 3 groups (n 
 5 each) on the basis of genotyping for the MDR1 gene, in a 4-dose study after single doses of digoxin alone (0.5 mg orally and intravenously) and coadministered with clarithromycin (400 mg orally for 8 days). The dose of digoxin was reduced during the clarithromycin phase (0.25 mg orally and intravenously). Results: The bioavailability of digoxin in G/G2677C/C3435, G/T2677C/T3435, and T/T2677T/T3435 subjects were 67.6%  4.3%, 80.9%  8.9%, and 87.1%  8.4%, respectively, and the difference between G/G2677C/C3435 and T/T2677T/T3435 subjects was statistically significant (P < .05). The MDR1 variants were also associated with differences in disposition kinetics of digoxin, with the renal clearance being almost 32% lower in T/T2677T/T3435 subjects (1.9  0.1 mL/min per kilogram) than G/G2677C/ C3435 subjects (2.8  0.3 mL/min per kilogram), and G/T2677C/T3435 subjects having an intermediate value 
TI - Role of human MDR1 gene polymorphism in bioavailability and interaction of digoxin, a substrate of P‐glycoprotein
JF - Clinical Pharmacology & Therapeutics
DO - 10.1067/mcp.2002.126177
DA - 2002-08-01
UR - https://www.deepdyve.com/lp/wiley/role-of-human-mdr1-gene-polymorphism-in-bioavailability-and-K77PERqPPB
SP - 209
EP - 219
VL - 72
IS - 2
DP - DeepDyve
ER -