Pharmacokinetics and pharmacodynamics of glyburide in young and elderly nondiabetic adults.
The pharmacokinetics and pharmacodynamics of glyburide were studied in elderly and young nondiabetic adults. Healthy nondiabetic men and women 18-40 years of age (young subjects) and 60-85 years of age (elderly subjects) were recruited. After an overnight fast, the subjects were given a baseline glucose tolerance test (GTT). The next day, again after a fast, each subject was given a 5-mg oral tablet of glyburide, and the GTT was performed one hour later. Serum glucose, serum insulin, and plasma glyburide concentrations were determined. Twenty elderly (mean +/- S.D. age, 65.7 +/- 5.3 years) male (n = 10) and female (n = 10) volunteers and 15 young (22.3 +/- 4.5 years) male volunteers were enrolled. Compared with the young subjects, the elderly subjects had slower glyburide absorption, as determined from a lower peak plasma concentration and smaller area under the plasma concentration-time curve from zero to four hours (AUC0-4). The elderly subjects also had a lower glyburide elimination rate constant and higher volume of distribution and a 52% higher free fraction. There was no difference in the glyburide AUC0-24 or AUC0-infinity or in oral clearance between the groups. The elderly group had greater increases in serum glucose and insulin concentrations after the baseline GTT. After glyburide administration, the elderly group had a smaller fractional decrease in the glucose AUC0-3 from the baseline GTT result than the young subjects. Linear regression analysis of the relationship between the fractional change in glucose concentration and the glyburide AUC0-4 showed significantly different slopes between the two groups. The aging process appears to affect the pharmacokinetics and pharmacodynamics of glyburide.
Schwinghammer
T L
TL
Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, PA 15261.
Antal
E J
EJ
Kubacka
R T
RT
Hackimer
M E
ME
Johnston
J M
JM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism*; D005215:Fasting / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test / Q000379:methods; D005905:Glyburide / Q000493:pharmacokinetics*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D005905:Glyburide