The influence of lamivudine, stavudine and nevirapine on the pharmacokinetics of chlorpropamide in human subjects.
Diabetic patients tend to be prone to infections, and multiple drug therapy cannot be ruled out in the management of diabetes. The effect of three routinely prescribed antiretroviral (ARV) drugs on the pharmacokinetic profile of an antidiabetic drug, chlorpropamide, was investigated in 18 human subjects, who had recently been diagnosed positive for human immunodeficiency virus (HIV) infection. The volunteers, aged 22-44 years and weighing 59-66 kg, were randomized into three groups with six subjects in each group. The study was carried out in two phases; in the first phase, all the subjects received chlorpropamide (250 mg) in a fasting state. In the second phase, the subjects received 250 mg of chlorpropamide together with lamivudine (150 mg) or stavudine (40 mg) or nevirapine (200 mg) in a fasting state. Chlorpropamide concentrations in the plasma were determined using a high performance liquid chromatography (HPLC) method developed earlier in our laboratory, while plasma glucose levels were determined using the standard glucose oxidase method. Lamivudine and stavudine decreased significantly (P < 0.05) the mean maximum plasma concentrations (Cmax) and the area under the plasma concentration-time curve (AUC(0-168h)) of chlorpropamide, while both drugs significantly increased the absorption half-life (t(1/2ab)) and elimination half-life (t(1/2el). the apparent volume of distribution (Vd) and the plasma clearance rate (Cl) of chlorpropamide (P < 0.05). The plasma glucose levels were also significantly increased between 0.5 - 4 h post dose (P < 0.05). However, it was found that the pharmacokinetic parameters of chlorpropamide and the blood glucose levels were not significantly altered by the co-administration with nevirapine.
Bakare-Odunola
M T
MT
Dept. of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Nigeria.
Enemali
I
I
Garba
M
M
Obodozie
O O
OO
Mustapha
K B
KB
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis; D002138:Calibration; D002747:Chlorpropamide / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics*; D019259:Lamivudine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D019829:Nevirapine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015203:Reproducibility of Results; D018119:Stavudine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D055815:Young Adult
D019380:Anti-HIV Agents; D001786:Blood Glucose; D065692:Cytochrome P-450 CYP3A Inhibitors; D007004:Hypoglycemic Agents; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D002747:Chlorpropamide