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目的 :在肿瘤患者中观察重组人肿瘤坏死因子α突变体rhTNF αD11a的药代动力学。方法 :在单次肌内注射 16 0× 10 4 U和 2 40× 10 4 U及连续肌内注射 16 0× 10 4 U ,qd× 7d后 ,用ELISA法测定其抗原浓度。结果 :方法学检验表明 ,灵敏度、特异性、线性、线性范围、精密度和回收率均符合要求。肌注 0 .5h后血清浓度显著高于内源水平 (P≤ 0 .0 5～ 0 .0 0 1) ,2 4h后多数患者恢复至药前水平。Cmax和AUC随剂量增高 ,平均Cmax分别为 10 .5和 14.7pg eq·mL-1,AUC分别为 5 0 .1和 10 6 .1pg eq·h·mL-1,但无统计学差异。Tmax随剂量有延长趋势。连续注射 7次后浓度明显低于首次注射 (P <0 .0 5 )。蓄积因子 (AUC第 7次/AUC第 1次)为 0 .6 5。结论 :在研究剂量范围内单次肌内注射药代动力学近似线性 ,连续注射后药物浓度呈降低趋势。
Objective: To observe the pharmacokinetics of rhTNFαD11a recombinant human tumor necrosis factor α mutant in patients with cancer. Methods: After a single intramuscular injection of 16 0 × 10 4 U and 2 40 × 10 4 U and continuous intramuscular injection of 16 × 10 4 U and qd × 7 d, the antigen concentration was determined by ELISA. Results: The methodological tests showed that the sensitivity, specificity, linearity, linearity range, precision and recovery meet the requirements. The intramuscular injection of 0.5h serum concentration was significantly higher than the endogenous level (P≤0.0 ~ 0.05), 24 hours after the majority of patients returned to pre-drug levels. Cmax and AUC increased with the dose, the average Cmax were 10 .5 and 14.7pg eq · mL-1, AUC were 50.1 and 106.1 pg eq · h · mL-1, but no significant difference. Tmax tends to increase with dose. After 7 consecutive injections, the concentration was significantly lower than that of the first injection (P <0.05). The accumulation factor (AUC 7th / AUC 1st) was 0.665. CONCLUSIONS: The pharmacokinetics of a single intramuscular injection was approximately linear over the study dose range, with a decreasing trend after continuous injection.