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.
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.
Authors: A Tornio; M Niemi; M Neuvonen; J Laitila; A Kalliokoski; P J Neuvonen; J T Backman Journal: Clin Pharmacol Ther Date: 2008-03-26 Impact factor: 6.875
Authors: Tanja Busk Bidstrup; Inga Bjørnsdottir; Ulla Grove Sidelmann; Mikael Søndergård Thomsen; Kristian Tage Hansen Journal: Br J Clin Pharmacol Date: 2003-09 Impact factor: 4.335
Authors: Mikko Niemi; Julian B Leathart; Mikko Neuvonen; Janne T Backman; Ann K Daly; Pertti J Neuvonen Journal: Clin Pharmacol Ther Date: 2003-10 Impact factor: 6.875
Authors: Mikko Niemi; Lauri I Kajosaari; Mikko Neuvonen; Janne T Backman; Pertti J Neuvonen Journal: Br J Clin Pharmacol Date: 2004-04 Impact factor: 4.335
Authors: Bhagwat Prasad; Raymond Evers; Anshul Gupta; Cornelis E C A Hop; Laurent Salphati; Suneet Shukla; Suresh V Ambudkar; Jashvant D Unadkat Journal: Drug Metab Dispos Date: 2013-10-11 Impact factor: 3.922