Toxicokinetics of propranolol enantiomers after a single intravenous dose of racemic propranolol in the rat
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Toxicokinetics of propranolol enantiomers after a single intravenous dose of racemic propranolol in the ratTranslated Title
[Toxicokinetiek van propranolol enantiomeren na een enkelvoudige intraveneuze dosis van racemisch propranolol in de rat.]Publiekssamenvatting
Abstract niet beschikbaarConscious male Wistar SPF Riv: TOX rats, body weight 275-300 g, were dosed intravenously with 2.5, 5 or 10 mg/kg racemic propranolol. HCl and plasma disposition of both S-(-)-propranolol and R-(+)-propranolol was followed for three hours. In all three dose groups plasma R-(+)- propranolol levels were initially higher than those of S-(-)-propranolol. Plasma S-(-)-propranolol showed significantly longer elimination half-life, longer mean residence time, larger volume of distribution, and higher total clearance than plasma R-(+)-propranolol. These differences can probably be explained by the known lower plasma protein binding of S-(-)-propranolol compared to R-(+)-propranolol. Disposition of S-(-)-propranolol after intravenous dosing of racemic propranolol was linear in the dose range examined. For R-(+)-propranolol a significant increase of volume of distribution with incresing dose was observed, but plasma elimination half-life, total clearance, and dose-normalized area under the plasma concentration-time curve were not dose-dependent.
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