Effect of ABCB1 haplotypes on the pharmacokinetics and renin-inhibiting effect of aliskiren.
OBJECTIVE
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.
Tapaninen
Tuija
T
Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, PO Box 705, 00029 HUS, Helsinki, Finland.
Neuvonen
Pertti J
PJ
Niemi
Mikko
M
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000577:Amides / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D005260:Female; D005650:Fumarates / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D006239:Haplotypes; D006801:Humans; D008297:Male; D000092502:Renin Inhibitors
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D000092502:Renin Inhibitors; C513055:ABCB1 protein, human; C446481:aliskiren