PHARMACOKINETICS OF ACEBUTOLOL ENANTIOMERS AFTER INTRAVENOUS ADMINISTRATION OF RACEMATE IN A RAT MODEL: A DOSING RANGE COMPARISON

✍ Scribed by S. ABOLFAZL MOSTAFAVI; ROBERT T. FOSTER

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 147 KB
• Volume: 18
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/(sici)1099-081x(199707)18:5<397::aid-bdd27>3.0.co;2-r

✦ Synopsis

Acebutolol (AC) is a chiral b-adrenergic blocking drug, possessing intrinsic sympathomimetic activity (ISA), and is useful clinically as the racemate in treating hypertension. Utilizing a stereospeci®c high-performance liquid chromatographic (HPLC) assay, the enantiomeric disposition of AC and its major metabolite diacetolol (DC) are reported after intravenous administration of single 5, 15, 30, and 50 mg kg 71 doses of racemate to male Sprague±Dawley rats. The mean area under the plasma concentration versus time curve (AUC) values display a linear relationship with respect to the administered dose. No statistical dierences are observed in apparent volume of distribution (V d ), terminal elimination half-life (t 1/2 ), total body clearance (Cl t ), or renal clearance (Cl r ) with respect to dose administered. Generally, R±S ratios for AUC following AC administration are statistically dierent from unity (p50´05). However, for the 50 mg kg 71 doses the R±S ratio for AUC is not statistically dierent from one. For DC, the plasma disposition is nonstereoselective in plasma. The amount of R-DC recovered in urine, however, was greater than that of the antipode (R:S=1´92+0´29). This study suggests that the enantiomeric disposition of intravenous AC is linear within the investigated range of 5±50 mg kg 71 racemate in rats. &1997 by John Wiley & Sons, Ltd.