RT Journal Article
SR Electronic
T1 Mechanism responsible for altered propranolol disposition in adjuvant-induced arthritis in the rat.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 482
OP 486
VO 14
IS 4
A1 K A Walker
A1 H E Barber
A1 G M Hawksworth
YR 1986
UL http://dmd.aspetjournals.org/content/14/4/482.abstract
AB Arthritis was induced in Sprague-Dawley rats by the injection of a heat-killed bacterial suspension into the right hind foot pad. The animals were deemed arthritic if their erythrocyte sedimentation rate was greater than 2 mm/hr. A pithed rat preparation was employed to investigate simultaneously the pharmacokinetics and pharmacodynamics of propranolol in this disease state. Propranolol administered via the hepatic portal vein to simulate oral administration resulted in elevated blood concentrations in the arthritic rats, but the pharmacological effect, measured by the inhibition of an electrically induced tachycardia, was not altered. Propranolol administered iv also resulted in increased blood drug concentrations, but, in addition, the pharmacological effect was decreased. Hepatic blood flow was determined in control and arthritic rats using radiolabeled microspheres, but no change was observed. These results, taken together with previous in vitro studies, suggest that the elevated blood concentrations of propranolol can be attributed to increased plasma protein binding, rather than to decreased hepatic metabolism or altered hepatic blood flow.