Effect of Experimental Diabetes Mellitus on the Pharmacokinetics of Atenolol Enantiomers in Rats

Abstract

The effect of streptozotocin-induced diabetes mellitus on the pharmacokinetics of the enantiomers of atenolol (AT) was investigated in rats 3 and 9 days after induction of the disease. Occurrence of diabetes was confirmed by a significant increase (p < 0.05) in the serum glucose concentration (mg%) of the diabetic rats compared with their respective controls in both 3- (441 ± 66.3 versus 181 ±31.3) and 9- (602 ± 133 versus 187 ± 20.0) day diabetic groups. Creatinine clearance (C/.cr; mL/min/kg) in 9-day diabetic rats (8.98 ± 3.02) was significantly higher than that in the controls (4.59 ± 1.08). However, compared with the control animals, the increase in CLcr of the 3-day diabetic rats (8.35 ± 1.95 versus 6.82 ± 1.63) was not significant (p > 0.05). The changes in CLcr paralleled those in renal clearance (CLr) values of the AT enantiomers; 9-day diabetes induced a significant increase in CL, of the AT enantiomers (82.4 and 81.6% increase for S(−)- and R(+(−enantiomers, respectively). An increase in CL, values of the AT enantiomers in 3-day diabetic rats, on the other hand, did not reach statistical significance. Furthermore, a significant increase (55.4 and 52.6% for S(−)- and fl(+)-AT, respectively) in the nonrenal clearance values of the AT enantiomers was observed in the 3-day, but not 9-day diabetic rats. The increases in the clearance values of the enantiomers of AT resulted in lower AUC values for the enantiomers in both the 3- and 9-day diabetic rats. Our results indicate that diabetes-induced kidney hyperfiltration in rats causes a significant increase in renal clearance of the AT enantiomers. Because AT is a recommended drug for control of hypertension in diabetic patients, further studies on the pharmacokinetics of the drug in diabetic patients are warranted.