Population Pharmacokinetics of Glyburide in Patients with Well-Controlled Diabetes

Study Objectives. To investigate glyburide pharmacokinetics in patients with well‐controlled noninsulin‐dependent diabetes mellitus (NIDDM), and test the hypothesis that intersubject variability in the glyburide dose is due to patient differences in the drug's pharmacokinetics. Methods. Prospective, open‐label study. Setting. University‐affiliated, internal medicine outpatient clinic. Patients. Fifty‐one patients with NIDDM (11 women, 40 men, mean age 56.7 ± 15.3 yrs) receiving oral glyburide and with well‐controlled glycohemoglobin levels 10.0% or below. Intervention. After fasting overnight, patients ingested their regular morning dose of glyburide and then ate breakfast. Blood samples were drawn before dosing and between 0.5–2 hours, 2–5 hours, and 5–10 hours after dosing. Measurements and Main Results. Serum glyburide was assayed by high‐performance 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.