LACK OF INTERACTION BETWEEN GLIPIZIDE AND COTRIMOXAZOLE

To identify the effects of co-trimoxazole on the elimination and dispo sition kinetics of glipizide, eight healthy male volunteers were studi ed in an unblinded, randomized, cross-over trial with two phases (no t reatment or co-trimoxazoIe 160/800 mg twice a day). During each phase, subjects were treated at home for 7 days with one of the treatment re gimens, followed by a 24-hour hospitalization for a single-dose challe nge with 10-mg oral glipizide and detailed blood studies. A 7-day wash out period was interspersed between the phases. Pharmacokinetic and ph armacodynamic parameters were determined and compared using the Studen t's t-test for paired observations. Glipizide area under the curve (AU C), clearance, and half life for treatment and control phases were 575 8 +/- 1874 versus 5176 +/- 1505 mu g/L/hour (P = .21), 0.41 +/- 0.15 v ersus 0.45 +/- 0.14 mL/min/kg (P = .27), and 5.13 +/- 2.10 versus 3.95 +/- 1.37 hours (P = .04), respectively. Twenty-four-hour glucose AUCs for treatment and control phases were 112.24 +/- 8.76 versus 114.86 /- 11.98 mmol/L/hour (P = .55), respectively. The only parameter reach ing statistical significance was glipizide half life, but the differen ce is of doubtful clinical significance because of difficulty in ident ifying a clear elimination phase in several subjects. It is concluded that co-trimoxazole administration did not significantly alter glipizi de disposition and elimination kinetics in this study population.