Article date: December 2008
By: Annikka Kalliokoski, Mikko Neuvonen, Pertti J. Neuvonen, Mikko Niemi, in Volume 66, Issue 6, pages 818-825
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
AIMS
To establish whether the effect of SLCO1B1[encoding organic anion transporting polypeptide 1B1 (OATP1B1)] c.521T→C (p.Val174Ala) polymorphism on the pharmacokinetics of repaglinide is dose‐dependent.
METHODS
Twelve healthy volunteers with the SLCO1B1 c.521TT genotype (controls) and eight with the c.521CC genotype ingested a single 0.25‐, 0.5‐, 1‐ or 2‐mg dose of repaglinide in a dose‐escalation study with a wash‐out period of ≥1 week.
RESULTS
The mean area under the plasma concentration–time curve from time 0 to infinity (AUC0–∞) of 0.25, 0.5, 1 or 2 mg repaglinide was 82% (95% confidence interval 47, 125), 72% (24, 138), 56% (24, 95) or 108% (59, 171) (P ≤ 0.001) larger in participants with the SLCO1B1 c.521CC genotype than in those with the c.521TT genotype, respectively. Repaglinide peak plasma concentration and AUC0–∞ increased linearly along with repaglinide dose in both genotype groups (r > 0.88, P < 0.001). There was a tendency towards lower blood glucose concentrations after repaglinide administration in the participants with the c.521CC genotype than in those with the c.521TT genotype.
CONCLUSIONS
The effect of SLCO1B1 c.521T→C polymorphism on the pharmacokinetics of repaglinide persists throughout the clinically relevant dose range.
DOI: 10.1111/j.1365-2125.2008.03287.x
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