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Aim:To study the in vivo and in vitro metabolism and the effect of para-toluene-sulfonamide (PTS) on cytochrome P450 enzymes (CYP450).Methods:Total CYP450and microsome protein content were determined after iv pretreatment of rats withPTS.CYP-specific substrates were incubated with rat liver microsomes.SpecificCYP isoform activities were determined by using HPLC.CYP chemical inhibitorsadded to the incubation mixture were used to investigate the principal CYP isoformsinvolved in PTS metabolism.The effect of PTS on CYP isoforms was investigatedby incubating PTS with specific substrates.Results:The groups treated with 33and 99 mg/kg per d PTS,respectively,had a total CYP content of 0.66±0.17 and0.60±0.12nmol/mg.The K_m and V_(max) were 92.2μmol/L and 0.0137nmol/min per mgprotein.CYP2C7,CYP2D1 and CYP3A2 might contribute to PTS metabolism in therat liver.The inhibitory effects of sulfaphenazole and ketoconazole on PTS me-tabolism were shown to have a mixed mechanism,whereas PTS metabolism wasinhibited noncompetitively by quinidine.PTS had little effect on the activities ofthe selected CYP isoforms.Conclusion:Generally speaking,it is relatively safefor PTS to be co-administered with other drugs.However,care should be takenwhen administering PTS with CYP inhibitors and the substrates of CYP2C,CYP2Dand CYP3A.
Aim: To study the in vivo and in vitro metabolism and the effect of para-toluene-sulfonamide (PTS) on cytochrome P450 enzymes (CYP450). Methods: Total CYP450 and microsome protein content were determined after iv pretreatment of rats with PTS. CYP-specific substrates were incubated with rat liver microsomes. SpecialCYP isoform activities were determined by using HPLC. CYP chemical inhibitors incorporated into the incubation mixture were used to investigate the principal CYP isoforms in regulated PTS metabolism. The effect of PTS on CYP isoforms was investigated by incubating PTS with specific substrates Results: The groups treated with 33 and 99 mg / kg per d PTS, respectively, had a total CYP content of 0.66 ± 0.17 and 0.60 ± 0.12 nmol / mg. Km and Vmax were 92.2 μmol / L and 0.0137 nmol / min per mgprotein.CYP2C7, CYP2D1 and CYP3A2 might contribute to PTS metabolism in therat liver. Inhibitory effects of sulfaphenazole and ketoconazole on PTS me-tabolism were shown to have a mixed mechanism, whereas PTS metabolis m was nothibited noncompetitively by quinidine. PTS had little effect on the activities of the selected CYP isoforms. Conclusions: Generally speaking, it is relatively safe for PTS to be co-administered with other drugs. substrates of CYP2C, CYP2D and CYP3A.