Citron M L, Reynolds J R, Lin W N, Frade P D, Schemansky M, Cohen M H, Krasnow S H, Johnston-Anderson A, Seltzer V L
Section of Medical Oncology, Long Island Jewish Medical Center, New Hyde Park, NY 11042.
Drug Intell Clin Pharm. 1987 Dec;21(12):981-5. doi: 10.1177/106002808702101211.
Four cancer patients with intractable pain received continuous morphine infusions in doses of 15-275 mg/h for a time period ranging from 4 to 27 days. Serum morphine concentrations were determined periodically following adjustments in infusion rates. As doses were changed and continued at static hourly rates, serum morphine concentrations were relatively constant 20 hours and beyond the time of the respective change, thus suggesting morphine elimination half-lives of less than or equal to 4 hours. High doses did not influence the time required to achieve steady-state concentrations. Steady serum morphine concentrations corresponded with hourly morphine doses in a parallel manner. High interpatient variabilities in clearances and steady-state serum morphine concentrations were noted. These data suggest that at morphine infusions up to 275 mg/h elimination pathways permit handling of increasing concentrations of morphine without nonlinear blood level increases. Also, marked interpatient and intrapatient variations in patient dose requirements were noted.
四名患有顽固性疼痛的癌症患者接受了持续吗啡输注，剂量为15 - 275毫克/小时，持续时间为4至27天。在调整输注速率后定期测定血清吗啡浓度。随着剂量改变并以固定的每小时速率持续输注，血清吗啡浓度在各自改变时间20小时及以后相对恒定，因此提示吗啡消除半衰期小于或等于4小时。高剂量并未影响达到稳态浓度所需的时间。稳态血清吗啡浓度与每小时吗啡剂量呈平行对应关系。注意到患者间清除率和稳态血清吗啡浓度存在高度变异性。这些数据表明，在高达275毫克/小时的吗啡输注情况下，消除途径能够处理不断增加的吗啡浓度，而不会使血药水平呈非线性增加。此外，还注意到患者间和患者内剂量需求存在显著差异。
