Analgesic and hyperthermic effects of intravenously administered morphine in the rat are related to its serum levels.
The analgesic response, colonic temperature changes and the pharmacokinetic parameters of i.v. administered morphine sulfate (2.5, 5.0 and 10.0 mg/kg) through indwelling cannulas in the jugular vein were determined in male Sprague-Dawley rats. The analgesic and hyperthermic responses were determined before and at 30-min intervals for a period of 360 min after the morphine injection and were expressed as area under the time-response curve. Blood samples were collected periodically for a period of 24 h. Serum was separated and was used for the estimation of morphine by the highly sensitive radioimmunoassay. The pharmacokinetic parameters, half life, the terminal elimination rate constant, the mean residence time, the apparent volume of distribution at steady state and the total clearance were determined by using noncompartmental analysis. The area under the serum concentration-time curve from time zero to infinity was related to the dose of morphine. The other parameters were the same for all the doses of morphine, except the serum levels of morphine extrapolated to zero time which increase gradually with the dose. Dose-dependent analgesic and hyperthermic responses were related to the area under the serum concentration-time curve. It is concluded that the dose-dependent pharmacological effects of morphine were related to the area under the serum concentration-time curve from time zero to infinity for serum levels of morphine but not to the other pharmacokinetic parameters.
Bhargava
H N
HN
Department of Pharmacodynamics, College of Pharmacy, University of Illinois, Chicago.
Villar
V M
VM
Gulati
A
A
Chari
G
G
D000698:Analgesia; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D009020:Morphine