Pharmacokinetics and pharmacodynamics of glyburide in young and elderly patients with non-insulin-dependent diabetes mellitus.

OBJECTIVE

To determine the influence of age on the pharmacokinetics and pharmacodynamics of glyburide after acute and chronic dosing in young and elderly subjects with non-insulin-dependent diabetes mellitus.

DESIGN

Ten elderly (mean age 69.3 +/- 3.1 y) and 10 younger (mean age 45.6 +/- 4.5 y) patients received a glucose challenge test at baseline, with a 2.5-mg dose of glyburide at week 0 (acute dose) and again at weeks 6 and 12 of chronic glyburide therapy. Glyburide doses were titrated to a maximum daily dosage of 20 mg to achieve a glucose concentration of 7.8 mmol/L or less. During 24-h pharmacokinetic determinations at weeks 0, 6, and 12, serial blood samples were obtained for glyburide determination with HPLC. Serial blood samples for glucose, insulin, and C-peptide determinations were obtained at baseline (week -1) and at weeks 0, 6, and 12.

RESULTS

All pharmacokinetic parameters assessed for glyburide were statistically comparable between the two age groups with the exception of a shorter time to peak concentration in the elderly at weeks 0 and 12. The glucose pharmacodynamic response to glyburide was not statistically different between the two groups. However, there was a statistically significant greater C-peptide response in the elderly group at all evaluation weeks.

CONCLUSIONS

Aging appears to have no influence on the pharmacokinetics of glyburide. Observed pharmacodynamic differences indicate the necessity for dosage titration to a specified therapeutic response regardless of patient age.