L A Jaber1, E J Antal, I R Welshman. 1. Department of Pharmacy Practice, Wayne State University, Detroit, MI 48201, USA.
Abstract
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.
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.