Catlin D H
J Pharmacol Exp Ther. 1977 Jan;200(1):224-35.
Two radioimmunoassays (RIA-A and RIA-B) were used to estimate morphine equivalents (ME) in rabbit serum after i.v. administration of morphine or morphine-3-glucuronide (M-3-G). RIA-A and RIA-B differed only with respect to the particular pool of antibodies used, and both were elicited from rabbits immunized with a 2-diazomorphine-protein conjugate. In vitro inhibition studies indicated the molar ratio of M-3-G/morphine which inhibited 3H-morphine-antimorphine binding by 50% (150) was 90 and 14 for RIA-A and RIA-B, respectively. RIA-B 150 values were dependent on the final protein concentration of the incubation mixture. RIA-A and RIA-B estimates of the ME per milliliter were in agreement in serum samples obtained from rabbits after i.v. morphine 0.01 mg/kg; however, after higher doses only samples obtained in the first minutes agreed and at later times RIA-B estimates exceeded RIA-A by increasing amounts. After i.v. M-3-G (1.0 mg/kg) RIA-B estimated 20 to 25 times more ME per milliliter than RIA-A. After rapid i.v. administration of morphine (1 or 5 mg/kg) the disappearance curves obtained with RIA-B were multiphasic and contained a prolonged terminal phase with an estimated half-life of 24 hours. The higher estimates obtained with RIA-B are best explained by cross-reactions with M-3-G or other morphine metabolites. With RIA-A the mean serum morphine clearance (86 ml/min/kg) and half-life of the elimination phase (74 minutes were independent of dosage. The least complicated pharmacokinetic model which describes the disposition of morphine in the rabbit is the open two-compartment model.
采用两种放射免疫分析法（放射免疫分析法A和放射免疫分析法B）来估计静脉注射吗啡或吗啡-3-葡萄糖醛酸苷（M-3-G）后兔血清中的吗啡当量（ME）。放射免疫分析法A和放射免疫分析法B仅在所用抗体的特定库方面有所不同，二者均由用2-重氮吗啡-蛋白质缀合物免疫的兔产生。体外抑制研究表明，对于放射免疫分析法A和放射免疫分析法B，使3H-吗啡-抗吗啡结合被50%抑制（IC50）的M-3-G/吗啡摩尔比分别为90和14。放射免疫分析法B的IC50值取决于孵育混合物的最终蛋白质浓度。对于静脉注射0.01 mg/kg吗啡后从兔获得的血清样本，每毫升ME的放射免疫分析法A和放射免疫分析法B估计值一致；然而，在更高剂量后，仅最初几分钟获得的样本一致，且在随后的时间里，放射免疫分析法B的估计值比放射免疫分析法A超出的量越来越大。静脉注射M-3-G（1.0 mg/kg）后，放射免疫分析法B估计每毫升的ME比放射免疫分析法A多20至25倍。快速静脉注射吗啡（1或5 mg/kg）后，用放射免疫分析法B获得的消失曲线呈多相，且包含一个延长的终末相，估计半衰期为24小时。放射免疫分析法B获得的较高估计值最好用与M-3-G或其他吗啡代谢物的交叉反应来解释。对于放射免疫分析法A，平均血清吗啡清除率（86 ml/min/kg）和消除相半衰期（74分钟）与剂量无关。描述吗啡在兔体内处置的最不复杂的药代动力学模型是开放二室模型。
