POPULATION PHARMACOKINETICS OF GLYBURIDE IN PATIENTS WITH WELL-CONTROLLED DIABETES

Study Objectives. To investigate glyburide pharmacokinetics in patient s with well-controlled noninsulin-dependent diabetes mellitus (NIDDM), and test the hypothesis that intersubject variability in the glyburid e dose is due to patient differences in the drug's pharmacokinetics. M ethods. Prospective, open-label study. Setting. University-affiliated, internal medicine outpatient clinic. Patients. Fifty-one patients wit h NIDDM (11 women, 40 men, mean age 56.7 +/- 15.3 yrs) receiving oral glyburide and with well-controlled glycohemoglobin levels 10.0% or bel ow. Intervention. After fasting overnight, patients ingested their reg ular morning dose of glyburide and then ate breakfast. Blood samples w ere drawn before dosing and between 0.5-2 hours, 2-5 hours, and 5-10 h ours after dosing. Measurements and Main Results. Serum glyburide was assayed by highperformance liquid chromatography and pharmacokinetics by NONMEM. Glyburide clearance was proportional to weight and greater in older patients (> 60 yrs). Conclusion. Variability in the glyburide dose was not primarily due to intersubject differences in the drug's pharmacokinetics.