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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Pharmacokinetics of histamine dihydrochloride in healthy volunteers and cancer patients: implications for combined immunotherapy with interleukin-2.
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Pharmacokinetics of histamine dihydrochloride in healthy volunteers and cancer patients: implications for combined immunotherapy with interleukin-2.

机译：组胺二盐酸盐在健康志愿者和癌症患者中的药代动力学：与白细胞介素2联合免疫治疗的意义。

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Recent clinical trials in melanoma and leukemia have demonstrated potential for increased survival time and improved remission when histamine dihydrochloride is added to cytokine monotherapy. In the present study, the pharmacokinetics of subcutaneous histamine (1 mg) in 21 healthy subjects and 12 melanoma patients was determined via model-dependent methods. Drug-drug interactions with subcutaneous interleukin-2 (1.1 mg) were evaluated in a combined cohort of patients with melanoma (n = 8) or renal cell carcinoma (n = 4). Histamine dihydrochloride administered over 10 minutes in healthy subjects peaked at 18 minutes (Cmax 38 nmol/L), attained a distribution volume of 59 L, and was eliminated at 6%/min. The results were similar in a 20-minute infusion in melanoma patients. No gender effects were observed (p > 0.05). Interleukin-2 injected either 10 minutes prior to or 10 minutes following histamine dihydrochloride had no effect on histamine kinetics. Histamine dihydrochloride administered 10 minutes prior to injection of interleukin-2 also had no effect on interleukin-2 kinetics. Maximal concentration of interleukin-2 (2,442 pg/ml) occurred at 2.5 hours with an elimination half-life of 1.7 hours, area under the curve (AUC) of 15,746 pg x h/ml, and volume of distribution and plasma clearance of 194 L and 74 L/h, respectively. However, interleukin-2 Cmax (1,758 pg/ml) and AUC (12,448 pg x h/ml) were reduced when histamine dihydrochloride was infused 10 minutes following interleukin-2, likely due to the pharmacodynamic effects of histamine, including increased heart rate and reduced blood pressure. It is concluded that histamine dihydrochloride and interleukin-2 can be safely coadministered with minimal interaction.
机译：最近在黑素瘤和白血病中进行的临床试验表明，将组胺二盐酸盐加入细胞因子单药治疗后，可以延长生存时间并改善缓解。在本研究中，通过模型依赖性方法确定了21名健康受试者和12名黑素瘤患者的皮下组胺（1毫克）的药代动力学。在黑色素瘤（n = 8）或肾细胞癌（n = 4）患者的联合队列中评估了与皮下白介素2（1.1 mg）的药物相互作用。在健康受试者中在10分钟内施用的组胺二盐酸盐峰值在18分钟时达到峰值（Cmax 38 nmol / L），达到59 L的分配体积，并以6％/ min的速度消除。黑色素瘤患者输注20分钟的结果相似。没有观察到性别影响（p> 0.05）。组胺二盐酸盐之前或之后10分钟注射的白细胞介素2对组胺动力学没有影响。在注射白介素2之前10分钟给予组胺二盐酸盐也对白介素2动力学没有影响。白细胞介素2的最大浓度（2,442 pg / ml）在2.5小时出现，消除半衰期为1.7小时，曲线下面积（AUC）为15,746 pg xh / ml，分布体积和血浆清除率为194 L和74 L / h。但是，在白介素2注射10分钟后注入盐酸组胺时，白介素2的Cmax（1,758 pg / ml）和AUC（12,448 pg xh / ml）降低了，这可能是由于组胺的药效学作用，包括心律加快和降低。血压。结论是，组胺二盐酸盐和白介素2可以安全地共同给药，且相互作用最小。

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