Multiple intramuscular injections: a major source of variability in analgesic response to meperidine.

Meperidine (ethidine) blood concentrations following multiple intramuscular injections (100 mg) over 2 days were determined in 10 female patients undergoing elective abdominal hysterectomies or cholecystectomies. Pain was estimated by subjective bioassay and the relationship between concentration and effect determined. The blood concentration-effect curve was steep with the range from no analgesia to complete analgesia being 0.35--0.45 microgram/ml on day 1 and 0.4--0.5 microgram/ml on day 2. The mean (+/- S.D.) minimum analgesic blood concentration was 0.5 +/- 0.1 microgram/ml (n = 32). Pain control was poor during the first 4-h dosing interval. The first injection post-surgery was also found to be the least representative of all subsequent injections. Blood concentrations fluctuated in phase with dosing interval, but were highly variable. Intra- and inter-patient peak concentrations varied by 2- and 5-fold and times taken to reach the peaks by 3- and 7-fold, respectively. Hence, meperidine blood concentrations were in excess of the minimum analgesic concentration for only about 35% of each of each 4-h dosing interval. Peak concentrations were not consistently correlated with body weight or lean tissue mass. Variable pain control following intermittent intramuscular meperidine injections was shown to be due to inadequate, fluctuating and unpredictable blood concentrations.