The pharmacokinetics and pharmacodynamics of 12 weeks of glyburide therapy in obese diabetics.
We have studied the pharmacokinetics and pharmacodynamics of glyburide during long-term therapy in 20 patients with type II diabetes mellitus. The patients were divided according to body mass index (BMI) into an obese group [n = 12, age 55(13) y, BMI 36.2(9.2) kg.m-2, total body weight (TBW) 100(23) kg], and a non-obese group [n = 8, age 61(13) y, BMI 24.5(2.1) kg.m-2, TBW 73(7) kg]. The dosages of glyburide were titrated to achieve specified therapeutic goals based upon serum glucose concentrations or to a maximum dosage of 20 mg per day. The pharmacokinetics of glyburide were determined at week 12 of treatment. On the study day, the patients took a 2.5 mg liquid test dose of glyburide with a Sustacal meal challenge. The elimination rate constant (lambda z), clearance (CL), and apparent volume of distribution (Vz) were 0.08 h-1, 3.3 l.h-1, and 47.0 l in the obese group, and 0.07 h-1, 3.1 l.h-1, and 56.8 l in the non-obese group. These values were not statistically significantly different. However, there were differences between the groups when the volume and clearance were corrected by TBW or BMI but not by ideal body weight (IBW) or fat-free mass (FFM). Regression analysis between the pharmacokinetic variables and body weight status revealed statistically significant correlations between volume or clearance and body weight. However, due to large inter-patient variability, these relations were relatively weak and were considered to be non-predictive.(ABSTRACT TRUNCATED AT 250 WORDS)
Jaber
L A
LA
Department of Pharmacy Practice, Wayne State University, Detroit, Michigan.
Antal
E J
EJ
Slaughter
R L
RL
Welshman
I R
IR
D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005905:Glyburide / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity; D013997:Time Factors
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005905:Glyburide