The clinical pharmacology of meperidine--comparison of routes of administration.

Abstract

The serum time-concentration curves and pharmacokinetic parameters of meperidine after the intravenous, intramuscular, and oral administration of 26 mg/m2 doses were determined and compared. After 30 minutes, there was no statistically significant difference between the serum time-concentration curve following intravenous administration and intramuscular administration; and after 2 hours, all three serum time-concentration curves were the same. Comparison of the mean cumulative excretion of meperidine and normeperidine following all three routes of administration demonstrated that the maxmimun rates of both meperidine and normeperidine reflect the route of administration, with a marked delay following oral administration reflecting a delay in absorption. Further, the excretion of normeperidene following oral administration, is greater despite adequate absorption than the other two routes of administration, indicating that delayed absorption increases the metabolic phase. Subjective symptomatology and the serum time-concentration curves were compared and their relationship wxamined. Comparison of the serum time-concentration curves to pervious analgesic and toxicity trials was made, and minimum serum levels for induction of analgesia and production of side effects are discussed. From the data it appears that in the case of acute pain, the intramuscular route of administration is as beneficial as the intravenous route, that oral dosing is less efficacious due to lower peak serum concentrations, and that all doses, regardless of the route administration, should be administered clinically on a mg/m2 basis rather than as a predetermined dose as currently used. Oral administration may have some benefit in the treatment of chronic pain, but the possibility of cumulative toxicity due to normeperidine should be considered.