Pharmacokinetics and pharmacodynamics of subcutaneous morphine pellets in the rat.

摘要: The pharmacokinetics and drug release characteristics of a standard, widely available s.c. morphine pellet were examined in the rat, together with antinociceptive (tailflick) effects physical dependence. Over 72-hr implant period one, two or three 75-mg pellets released 12.5, 22.6 27.6 mg morphine, respectively. Mean plasma concentration after reached peak at 4 to 6 hr, then declined mean apparent steady-state level 210 ng/ml 36 hr that was maintained until removed 72 hr. action peaked had returned predrug base-line values by After removal, elimination kinetics biexponential terminal T1/2 8.3 85% before onset significant weight loss could be measured. Peak abstinence dose-related significantly correlated both levels just withdrawal total dose absorbed over implant. These studies indicate from implanted rat is characterized an initially higher rate (dose dumping effect) first 24 followed very constant implantation. pharmacodynamic consequences these dosage are rapid development tolerance maintenance dependence during