Oral and intravenous pharmacokinetics of metformin with and without oral codeine intake in healthy subjects - a cross-over study
| Autor: | Amanda Nøddebo Nyrup, Ida Kuhlmann, Kim Brøsen, Flemming Nielsen, Kurt Højlund, Per Damkier, Troels K Bergmann, Tore Bjerregaard Stage, Mette Marie Hougaard Christensen |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adult
CYP2D6 endocrine system diseases RM1-950 Pharmacology General Biochemistry Genetics and Molecular Biology Article Young Adult Pharmacokinetics medicine Humans General Pharmacology Toxicology and Pharmaceutics Cross-Over Studies Morphine business.industry Codeine General Neuroscience Research digestive oral and skin physiology nutritional and metabolic diseases General Medicine Articles Drug interaction Crossover study Healthy Volunteers Metformin Analgesics Opioid Concomitant Therapeutics. Pharmacology Public aspects of medicine RA1-1270 business Algorithms medicine.drug |
| Zdroj: | Kuhlmann, I, Nyrup, A N, Stage, T B, Christensen, M M H, Bergmann, T K, Damkier, P, Nielsen, F, Højlund, K & Brøsen, K 2021, ' Oral and intravenous pharmacokinetics of metformin with and without oral codeine intake in healthy subjects-a cross-over study ', Clinical and Translational Science, vol. 14, no. 6, pp. 2408-2419 . https://doi.org/10.1111/cts.13107 Clinical and Translational Science Clinical and Translational Science, Vol 14, Iss 6, Pp 2408-2419 (2021) |
| Popis: | The aim of the study was to investigate if there is a clinically relevant drug interaction between metformin and codeine. Volunteers were randomized to receive on four separate occasions: (A) orally administered metformin (1 g), (B) intravenously administered metformin (0.5 g), (C) five doses of tablet codeine 25 mg; the last dose was administered together with oral metformin (1 g), and (D) five doses of tablet codeine 25 mg; the last dose was administered together with metformin (0.5 g) intravenously. Blood samples were drawn for 24 h after administration of metformin, and for 6 h after administration of codeine and analyzed using liquid chromatography and tandem mass spectrometry. Healthy volunteers genotyped as CYP2D6 normal metabolizers (*1/*1) without known reduced function variants in the OCT1 gene (rs12208357, rs34130495, rs34059508, and rs72552763) were invited. The median absorption fraction of metformin was 0.31 and was not influenced by codeine intake. The median time to maximum concentration ((Formula presented.)) after oral intake of metformin was 2 h without, and 3 h with codeine (p = 0.06). The geometric mean ratios of the areas under the plasma concentration time-curve (AUCs) for morphine and its metabolites M3G and M6G for oral intake of metformin-to-no metformin were 1.21, 1.31, and 1.27, respectively, and for i.v. metformin-to-no metformin 1.28, 1.34, and 1.30, respectively. Concomitant oral and i.v. metformin increased the plasma levels of morphine, M3G and M6G. These small pharmacokinetic changes may well contribute to an increased risk of early discontinuation of metformin. Hence, a clinically relevant drug-drug interaction between metformin and codeine seems plausible. |
| Databáze: | OpenAIRE |
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