A DRUG-INTERACTION STUDY BETWEEN CICLETANINE AND TOLBUTAMIDE IN HEALTHY-VOLUNTEERS

Objective: To determine the possible interaction between the antihyper tensive agent cicletanine and the hypoglycaemic drug tolbutamide. Meth ods: Time-courses of glycaemia and serum immunoreactive insulin (IRI) were followed in 10 healthy subjects after two tolbutamide infusions i n each volunteer: initially alone and 9 days later concomitantly with repeated oral cicletanine. Any drug interaction was quantified on the basis of a decrease or increase in the AUC with time of glycaemia and IRI by subtraction of baseline concentration (AUC(0)(240)-GLY and AUC( 0)(60)-IRI). Peak glycaemia and peak IRI, and the corresponding time t o peaks, were also assessed. Results: Following tolbutamide, mean AUC( 0)(240)-GLY values were 97.7 and 98.8 mmol . l(-1) . min, without or w ith cicletanine, respectively; the corresponding AUC(0)(60)-IRI were 4 85 and 321 mU . l(-1) . min. Mean peak glycaemia values were 0.996 and 1.071 mmol . l(-1). Regarding the peak IRI, a decrease was observed a fter tolbutamide and cicletanine: median values were 29.2 and 17.4 mU . l(-1). The corresponding median time to peak of glycaemia and TRI va lues were 30 and 30 min, and 5 (all subjects) and 5 min. Conclusion: N o clinically relevant interaction was shown after the concomitant admi nistration of repeated oral doses of cicletanine and acute intravenous tolbutamide to healthy volunteers.