Lack of interaction between glipizide and co-trimoxazole

To identify the effects of co-trimoxazole on the elimination and disposition kinetics of glipizide, eight healthy male volunteers were studied in an unblinded, randomized, cross-over trial with two phases (no treatment or co-trimoxazole 160/800 mg twice a day). During each phase, subjects were treated at home for 7 days with one of the treatment regimens, followed by a 24-hour hospitalization for a single-dose challenge with 10-mg oral glipizide and detailed blood studies. A 7-day washout period was interspersed between the phases. Pharmacokinetic and pharmacodynamic parameters were determined and compared using the Student's t-test for paired observations. Glipizide area under the curve (AUC), clearance, and half life for treatment and control phases were 5758 +/- 1874 versus 5176 +/- 1505 micrograms/L/hour (P = .21), 0.41 +/- 0.15 versus 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 reaching statistical significance was glipizide half life, but the difference is of doubtful clinical significance because of difficulty in identifying a clear elimination phase in several subjects. It is concluded that co-trimoxazole administration did not significantly alter glipizide disposition and elimination kinetics in this study population.