| Abstract: | Abstract— Turpentine oil treatment (0·2 mL kg?1, s.c.) was used to increase the plasma concentration of α1-acid glycoprotein (0·13 mg mL?1 in control rats) to 1·72 mg mL?1 after 2 days, and allow assessment of its effects on the pharmacokinetics and stereoselective binding of three β-blockers. Racemates (5 mg kg?1) were administered intravenously to control and turpentine oil-pretreated rats and the plasma concentrations were determined up to 90 min. Stereoselective analysis showed the apparent distribution volume and the area under plasma concentration-time curves (AUC) of R-(+)-propranolol to be, respectively, one-quarter and twice those of the S-(–)-enantiomer and differences in pharmacokinetic parameters between the two were magnified by turpentine oil pretreatment. Pharmacokinetic parameters of oxprenolol enantiomers were essentially similar for the controls but after turpentine oil pretreatment, a higher affinity of the R-(+)-enantiomer for plasma was observed. Acebutolol enantiomers behaved non-stereospecifically throughout. These results were consistent with predictions from the in-vitro stereospecific binding properties of these agents to purified rat α1-acid glycoprotein. |
