A drug interaction study between cicletanine and tolbutamide in healthy volunteers.

OBJECTIVE

To determine the possible interaction between the antihypertensive agent cicletanine and the hypoglycaemic drug tolbutamide.

METHODS

Time-courses of glycaemia and serum immunoreactive insulin (IRI) were followed in 10 healthy subjects after two tolbutamide infusions in 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 (AUC0(240)-GLY and AUC0(60)-IRI). Peak glycaemia and peak IRI, and the corresponding time to peaks, were also assessed.

RESULTS

Following tolbutamide, mean AUC0(240)-GLY values were 97.7 and 98.8 mmol.l-1.min, without or with cicletanine, respectively; the corresponding AUC0(60)-IRI were 485 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 after tolbutamide and cicletanine: median values were 29.2 and 17.4 mU.l-1. The corresponding median time to peak glycaemia and IRI values were 30 and 30 min and 5 (all subjects) and 5 min.

CONCLUSION

No clinically relevant interaction was shown after the concomitant administration of repeated oral doses of cicletanine and acute intravenous tolbutamide to healthy volunteers.