Using a limited sampling strategy to investigate the interindividual pharmacokinetic variability in metformin: A large prospective trial.

Autor: Kuhlmann I; Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark., Arnspang Pedersen S, Skov Esbech P; Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark., Bjerregaard Stage T; Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark., Hougaard Christensen MM; Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.; Department of Clinical Research, University of Southern Denmark, Odense, Denmark., Brøsen K; Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.; OPEN, Odense Patient data Explorative Network, Odense University Hospital, Odense, Denmark.
Jazyk: angličtina
Zdroj: British journal of clinical pharmacology [Br J Clin Pharmacol] 2021 Apr; Vol. 87 (4), pp. 1963-1969. Date of Electronic Publication: 2020 Nov 13.
DOI: 10.1111/bcp.14591
Abstrakt: Aims: Recently a limited sampling strategy (LSS) for determination of metformin' pharmacokinetics was developed. The LSS utilizes the plasma concentration of metformin 3 and 10 hours after oral intake of a single dose to estimate the area under the concentration-time curve up to 24 hours (AUC 0-24h ). The main purpose of this study was to support the feasibility of this strategy in a large prospective trial.
Methods: Volunteers orally ingested two 500-mg tablets of metformin hydrochloride. A blood sample was drawn three and ten hours after the ingestion. Urine was collected for 0-10 and 10-24 hours and urine volumes recorded. The AUC 0-24h was calculated using the equation AUC 0-24h = 4.779 * C 3 + 13.174 * C 10 . Additionally, all participants were genotyped for the single-nucleotide polymorphism A270S in OCT2, g.-66 T > C in MATE1, R61C, G465R, G401S and the deletion M420del in OCT1.
Results: In total, 212 healthy volunteers participated. The median (25th - 75th interquartile range) AUC 0 - 24h , CL renal , C 3 and C 10 , were 10 600 (8470-12 500) ng* hr* mL -1 , 29 (24-34) L* hour -1 , 1460 (1180-1770) and 260 (200-330) ng* mL -1 , respectively, which is in agreement with our previous results. GFR i was correlated with metformin AUC and CL renal (P < .001). As expected, we found a great pharmacokinetic interindividual variability among the volunteers and no effect of the OCT1 genotype on the AUC 0 - 24h . We were unable to reproduce our previous finding of a gene-gene interaction (OCT2 and MATE1) effect on CL renal in this cohort.
Conclusion: This study further supports the use of the 2-point LSS algorithm in large pharmacokinetic trials.
(© 2020 British Pharmacological Society.)
Databáze: MEDLINE
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