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.


CONCLUSIONS
No clinically relevant interaction was shown after the concomitant administration of repeated oral doses of cicletanine and acute intravenous tolbutamide to healthy volunteers.
Bayés
M C
MC
Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Department of Pharmacology and Psychiatry, Autonomous University of Barcelona, Spain.
Barbanoj
M J
MJ
Vallès
J
J
Torrent
J
J
Obach
R
R
Jané
F
F
D000284:Administration, Oral; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D008297:Male; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D014044:Tolbutamide / Q000008:administration & dosage / Q000494:pharmacology*
D000959:Antihypertensive Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D011725:Pyridines; D014044:Tolbutamide; C038068:cicletanine