Austin K L, Stapleton J V, Mather L E
Department of Anaesthesia and Intensive Care, Flinders Medical Centre, The Flinders University of South Australia, Bedford Park 5042, Australia.
Pain. 1980 Feb;8(1):47-62. doi: 10.1016/0304-3959(80)90089-5.
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.
对10例行择期腹部子宫切除术或胆囊切除术的女性患者，测定了她们在2天内多次肌内注射（100毫克）哌替啶（乙基哌替啶）后的血药浓度。通过主观生物测定法评估疼痛程度，并确定浓度与效果之间的关系。血药浓度-效应曲线较陡，第1天从无镇痛作用到完全镇痛的血药浓度范围为0.35--0.45微克/毫升，第2天为0.4--0.5微克/毫升。平均（±标准差）最小镇痛血药浓度为0.5±0.1微克/毫升（n = 32）。在最初的4小时给药间隔内，疼痛控制不佳。还发现术后第一次注射最不能代表所有后续注射情况。血药浓度随给药间隔呈同步波动，但个体差异很大。患者体内和患者之间的血药峰浓度相差2倍和5倍，达到峰浓度的时间相差3倍和7倍。因此，在每4小时的给药间隔中，哌替啶血药浓度仅约35%的时间超过最小镇痛浓度。血药峰浓度与体重或瘦体重之间无一致的相关性。间歇性肌内注射哌替啶后疼痛控制情况不一，这表明是由于血药浓度不足、波动且不可预测所致。
