Cotrimoxazole as an inhibitor of oxidative drug metabolism: effects of trimethoprim and sulphamethoxazole separately and combined on tolbutamide disposition.
Open Access
- 1 November 1985
- journal article
- research article
- Published by Wiley in British Journal of Clinical Pharmacology
- Vol. 20 (5) , 482-485
- https://doi.org/10.1111/j.1365-2125.1985.tb05102.x
Abstract
The effect of separate pretreatments with cotrimoxazole, sulphamethoxazole and trimethoprim on the disposition of tolbutamide was studied in seven healthy males. Tolbutamide 500 mg intravenously was administered on four separate occasions‐as a control without pretreatment and on the seventh day of separate twice daily administration of cotrimoxazole (sulphamethoxazole 800 mg plus trimethoprim 160 mg) (ST phase), sulphamethoxazole 1 g (S phase) and trimethoprim 150 mg (T phase). Tolbutamide total and unbound plasma clearance (CL) were reduced following each of the individual pretreatments compared to the control phase (P less than 0.001). For unbound CL the reductions were 14% in the S and T phases and 25% in ST phase. Tolbutamide elimination half‐life was prolonged following each pretreatment (P less than 0.001) by 20% in the S phase, 19% in the T phase and 30% in the ST phase. Tolbutamide total steady‐state volume of distribution (VSS) was increased by 10% in the S and ST phases (P less than 0.01), the increase being accounted for by an increase in tolbutamide unbound fraction. There was no change in tolbutamide unbound VSS following any of the pretreatments. These results are consistent with inhibition of tolbutamide oxidation by cotrimoxazole, an additive effect of the two components sulphamethoxazole and trimethoprim. Sulphamethoxazole also reduces tolbutamide plasma protein binding.This publication has 9 references indexed in Scilit:
- The effect of sulphinpyrazone on oxidative drug metabolism in man: Inhibition of tolbutamide eliminationEuropean Journal of Clinical Pharmacology, 1982
- Stereoselective Interaction of Trimethoprim-Sulfamethoxazole with the Separated Enantiomorphs of Racemic Warfarin in ManNew England Journal of Medicine, 1980
- Clinical Pharmacokinetics of Co-trimoxazole (trimethoprim-sulphamethoxazole)Clinical Pharmacokinetics, 1980
- Noncompartmental Determination of the Steady‐State Volume of DistributionJournal of Pharmaceutical Sciences, 1979
- The Effect of Different Sulfonamides on Phenytoin Metabolism in ManActa Medica Scandinavica, 1979
- Simple, rapid and micro high-pressure liquid chromatographic method for the simultaneous determination of tolbutamide and carboxy tolbutamide in plasmaJournal of Chromatography B: Biomedical Sciences and Applications, 1978
- Effect of trimethoprim-sulfamethoxazole on blood insulin and glucose concentrations of diabetics.1975
- The Metabolic Fate of Tolbutamide in Man and in the RatJournal of Medicinal Chemistry, 1966