Related Experiment Videos
The effect of SLCO1B1 polymorphism on repaglinide pharmacokinetics persists over a wide dose range
Annikka Kalliokoski1, Mikko Neuvonen, Pertti J Neuvonen
1Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
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 > or =1 week.
Results:
The mean area under the plasma concentration-time curve from time 0 to infinity (AUC(0-infinity)) 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 < or = 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 AUC(0-infinity) 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.
Related Concept Videos
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
Pharmacogenetics of Drug Metabolism: Overview
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
A study on guinea pigs examined the...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Oral Hypoglycemic Agents: Glinides
Pharmacokinetic–Pharmacodynamic Relationship: Duration of Dose-Effect Relationship