Pharmacokinetics and local responses to submucosal meperidine compared with other routes of administration

Abstract

The objective of this study was to determine the time course of the plasma levels of meperidine administered by various routes. Ten healthy adults received 0.8 mg/kg of meperidine given intravenous, submucosal, intramuscular, and 1.4 mg/kg orally in a randomized sequence at a minimum of one-week intervals. Blood samples were collected at 0, 10, 20, 30, 45, 60, 90, 120, 180, 240, 360, and 720 min. The plasma was separated by centrifugation at room temperature. Plasma samples were analyzed for unchanged meperidine by a high-pressure liquid chromatographic assay. Pharmacokinetic parameters were calculated according to standard techniques. Data analysis was accomplished using a 4 x 11 analysis of variance and the Scheffe test for multiple comparisons. Pain response and tissue changes also were assessed using 4-point scales. Significant interaction effects (P < 0.00001) were found between the administration route and the time intervals. The maximum observed concentration of meperidine for the IV and SM routes occurred at the first sample point at 10 min, for the IM route at 20 min, and for the PO route at 45 min. There were no significant differences between the IV and the SM routes at any time interval measured. Post hoc comparisons of the peak values demonstrated significant differences between the IM and PO values (1.4 mg/kg) when compared with the IV and SM routes (P < 0.01). SM route caused greater tissue response and pain reaction, however, the differences were not statistically significant.