Toxicokinetics of a single intravenous dose of rac-propranolol versus optically pure propranolol in the rat

Chirality
W BodeD J de Wildt

Abstract

Conscious male Wistar SPF Riv:TOX rats were dosed intravenously with 2.5, 5, or 10 mg/kg rac-propranolol.HCl, or with 5 mg/kg of either (-)-(S)- or (+)-(R)-propranolol.HCl. Disposition of (-)-(S)- and (+)-(R)-propranolol after dosing of rac-propranolol was linear in the dose range examined. Total plasma clearance was not changed in animals dosed with the individual enantiomers compared to the animals that were dosed with rac-propranolol. However, for (-)-(S)-propranolol both volume of distribution and elimination half-life decreased, whereas for (+)-(R)-propranolol increases were observed for these characteristics, in animals dosed with the individual enantiomers. Our observations suggest that the (+)-(R)-enantiomer competes with (-)-(S)-propranolol for plasma protein binding sites, resulting in lower plasma protein binding of the (-)-(S)-enantiomer when the racemate is administered. From recent toxicological experiments, it was concluded that rac-propranolol is more toxic than the individual enantiomers in the rat, when dosed iv at the same total mass. It is concluded that the observed potentiation of toxic effects of propranolol enantiomers when administered as a racemate can at least partly be explained by a pharmacokinetic ...Continue Reading

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Citations

Mar 11, 2008·Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics·Sanda Mihaela PopescuFlorica Popescu
Mar 18, 2004·The Journal of Pharmacy and Pharmacology·Wenhui LinNobuo Inotsume
Jul 27, 2006·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·H LuK K Chan
May 6, 2003·Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons·Theodosios SaranteasChristina Tesseromatis

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