Effect of experimental diabetes mellitus on the pharmacokinetics of atenolol enantiomers in rats

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 less than 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 (CLcr; 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 greater than 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 CLr of the AT enantiomers (82.4 and 81.6% increase for S(-)-and R(+)-enantiomers, respectively). An increase in CLr 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 R(+)-AT, respectively) in the nonrenal clearance values of the AT enantiomers was observed in the 3-day, but not 9-day diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)