Tuija Tapaninen1, Pertti J Neuvonen, Mikko Niemi. 1. Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, PO Box 705, 00029 HUS, Helsinki, Finland.
Abstract
PURPOSE: This study aimed to investigate the possible effects of ABCB1 haplotypes on the pharmacokinetics and renin-inhibiting effect of aliskiren. METHODS: Eleven healthy volunteers homozygous for the ABCB1 c.1236C-c.2677G-c.3435C (CGC) haplotype and 11 homozygous for the c.1236T-c.2677T-c.3435T (TTT) haplotype ingested a single 150-mg dose of aliskiren. Plasma aliskiren concentrations were measured up to 72 h, its excretion into urine up to 12 h, and plasma renin activity up to 24 h. RESULTS: The ABCB1 haplotypes had no significant effect on the pharmacokinetics or renin-inhibiting effect of aliskiren. The geometric mean ratio (95% confidence interval) of aliskiren peak plasma concentration and area under the plasma concentration-time curve from 0 h to infinity in participants homozygous for the TTT haplotype to those in participants homozygous for the CGC haplotype were 1.14 (0.66, 1.96; P = 0.631) and 1.01 (0.58, 1.76; P = 0.960) respectively. CONCLUSIONS: These data suggest that the ABCB1 c.1236C-c.2677G-c.3435C and c.1236T-c.2677T-c.3435T haplotypes have no clinically meaningful effect on the pharmacokinetics of aliskiren.
PURPOSE: This study aimed to investigate the possible effects of ABCB1 haplotypes on the pharmacokinetics and renin-inhibiting effect of aliskiren. METHODS: Eleven healthy volunteers homozygous for the ABCB1c.1236C-c.2677G-c.3435C (CGC) haplotype and 11 homozygous for the c.1236T-c.2677T-c.3435T (TTT) haplotype ingested a single 150-mg dose of aliskiren. Plasma aliskiren concentrations were measured up to 72 h, its excretion into urine up to 12 h, and plasma renin activity up to 24 h. RESULTS: The ABCB1 haplotypes had no significant effect on the pharmacokinetics or renin-inhibiting effect of aliskiren. The geometric mean ratio (95% confidence interval) of aliskiren peak plasma concentration and area under the plasma concentration-time curve from 0 h to infinity in participants homozygous for the TTT haplotype to those in participants homozygous for the CGC haplotype were 1.14 (0.66, 1.96; P = 0.631) and 1.01 (0.58, 1.76; P = 0.960) respectively. CONCLUSIONS: These data suggest that the ABCB1c.1236C-c.2677G-c.3435C and c.1236T-c.2677T-c.3435T haplotypes have no clinically meaningful effect on the pharmacokinetics of aliskiren.
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