Journal
CLINICA CHIMICA ACTA
Volume 359, Issue 1-2, Pages 46-52Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.cccn.2005.03.010
Keywords
MDRI; genotype; absorption; talinolol
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Objective: We investigated the linkage between SNPs in exon 12 (C1236T), exon 21 (G2677T/A) and exon 26 (C3435T) of MDR1, and explored the effect of linked polymorphism on the absorption of talinolol after a single oral dose of 100 mg. Methods: The genotype of 192 healthy Chinese volunteers was determined using PCR-RFLP with respect to the MDR1 alleles of interest, C1236T, G2677T/A and C3435T. Linkage disequilibrium was analyzed using PHASE software. Consecutive eligible subjects received a single oral dose of 100 mg talinolol. Venous blood samples were taken at intervals up to 60 h post dose for HPLC analysis of plasma concentration of talinolol to obtain a pharmacokinetic profile. Results: Linkage disequilibrium existed between exon 21 (G2677T/A) and exon 26 (C3435T), exon 12 (C1236T) and exon 21 (G2677T/A), but not between exon 12 (C1236T) and exon 21 (G2677T/A). AUC (0,3h), AUC (0,infinity), C-max and C-max/AUC (0,00), used as indices of talinolol absorption, were not significantly different between the genotype groups of 2677GG/3435TT, 2677TT/3435TT, 2677GT/3435CT and 2677AT/3435CT. For these 4 groups, AUC(0,3h) were 436.8 +/- 50.1, 510.1 +/- 86.3, 466.1 +/- 77.8 and 437.2 +/- 73.4 (mu g x h/l) and the C-max/AUC (0, infinity) were 0.097 +/- 0.018, 0.093 +/- 0.022, 0.105 +/- 0.014 and 0.102 +/- 0.027 (h(-1)), respectively. (P > 0.05). Conclusions: The linked MDR1 polymorphisms in exon 21 G2677T/A and exon 26 C3435T apparently did not contribute to the absorptive pharmacokinetics of a single oral dose of 100 mg talinolol. (c) 2005 Elsevier B.V All rights reserved.
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