Abstract
The pharmacokinetics of R - and S-atenolol after intravenous administration of racemic atenolol were studied in 3-, 12- and 24-month-old rats and in 3-month-old rats with renal failure induced by uranyl nitrate. In all age groups, the area under the plasma concentration-time curves is higher for R- than for S-atenolol; volume of distribution, total clearance and renal clearance are lower for R-atenolol than for S-atenolol, but the differences are small. In function of age there is for both enantiomers a significant increase in AUC, due, at least in part, to a decreased renal clearance; the effect of aging is not stereoselective. In rats with renal failure, the AUC of both enantiomers increases, due mainly to a decrease in renal clearance, but to a lesser degree also to a decrease in nonrenal clearance. For both enantiomers, the volume of distribution decreases and the half-life increases in the uraemic rats. The total amount of both enantiomers excreted in the urine is decreased in the rats with renal failure. There are no stereoselective effects of treatment of the rats with uranyl nitrate.
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