Bode W ,
Groen C ,
Poelen MJ ,
Arens ABM ,
Beenen J ,
Stolker AAM ,
Ginkel LA van ,
Toet AE ,
Wemer J ,
Wildt DJ de
19 p
in Dutch
1993
Toon Nederlands
English Abstract Conscious 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.
