Because physiological changes occurring in
diabetes mellitus patients could alter the pharmacokinetics and pharmacodynamics of the drugs used to treat the disease, the pharmacokinetics and pharmacodynamics of
azosemide were investigated after intravenous and
oral administration of the
drug (10 mg kg-1) to control and
alloxan-induced
diabetes mellitus rats (AIDRs). After
intravenous administration of
azosemide to the AIDRs, the area under the plasma concentration-time curve (AUC) increased considerably (3120 compared with 2520 micrograms min mL-1; P < 0.135) and the total body clearance decreased considerably (3.20 compared with 3.96 mL min-1 kg-1; P < 0.0593). The considerable reduction in time-averaged total body clearance in the AIDRs was a result of the significant decrease in renal clearance (1.01 compared with 1.55 mL min-1 kg-1) in the AIDRs, the non-renal clearance being comparable between the two groups of rats. After
intravenous administration, the 8-h urinary excretion of
azosemide (29.5 compared with 40% of intravenous dose; P < 0.0883) and one of its metabolites, M1 (2.15 compared with 2.60% of intravenous dose, expressed in terms of
azosemide; P < 0.05) decreased in the AIDRs because of the impaired kidney function. The
diuretic, natriuretic, kaliuretic and chloruretic efficiencies increased significantly in the AIDRs. After
oral administration of
azosemide, AUC decreased significantly in the AIDRs (115 compared with 215 micrograms min mL-1) possibly because of the reduced gastrointestinal absorption of
azosemide in the AIDRs. After
oral administration of
azosemide, the 8-h urine output decreased significantly in the AIDRs (9.32 compared with 16.1 mL per 100 g
body weight) because of the significantly reduced 8-h urinary excretion of
azosemide (3.00 compared with 9.14% of oral dose). After both intravenous and
oral administration some pharmacokinetic and pharmacodynamic parameters of
azosemide were significantly different in AIDRs.