Chiang J, Gloff C A, Yoshizawa C N, Williams G J
Department of Toxicology/Clinical Pharmacology, Berlex Laboratories, Richmond, California 94806.
Pharm Res. 1993 Apr;10(4):567-72. doi: 10.1023/a:1018902120023.
The pharmacokinetics of and biologic response modification by recombinant human interferon-beta ser (rIFN-beta ser) were evaluated in 12 healthy male volunteers. Subjects received a single intravenous (iv) injection of 90 x 10(6) IU of rIFN-beta ser followed by a single or eight consecutive daily 90 x 10(6) IU subcutaneous (sc) doses. Blood samples collected after the iv, first sc, and last sc doses and prior to each sc dose were assayed for interferon antiviral activity and the interferon-inducible marker neopterin. Following iv administration, serum interferon concentrations generally declined biexponentially, with a mean serum clearance of 0.76 +/- 0.28 L/hr-kg, a mean steady-state volume of distribution of 2.88 +/- 1.81 L/kg, and a mean terminal half-life of 4.29 +/- 2.29 hr as determined by noncompartmental analysis. Following sc administration, absorption of rIFN-beta ser was prolonged, with serum concentrations generally below 100 IU/mL. No accumulation of rIFN-beta ser in serum was noted after eight daily sc injections. In contrast, serum neopterin levels did not increase above baseline levels until 12 hr after iv dosing and 24 hr after sc dosing. The mean increase in serum neopterin at 24 hr post iv injection was significantly greater than that at 24 hr post sc dosing.
在12名健康男性志愿者中评估了重组人干扰素-β1a（rIFN-β1a）的药代动力学及生物反应修饰作用。受试者接受单次静脉注射90×10⁶ IU的rIFN-β1a，随后接受单次或连续8天每天90×10⁶ IU的皮下注射。在静脉注射、首次皮下注射和末次皮下注射后以及每次皮下注射前采集血样，检测干扰素抗病毒活性和干扰素诱导标志物新蝶呤。静脉给药后，血清干扰素浓度一般呈双指数下降，通过非房室分析确定，平均血清清除率为0.76±0.28 L/（小时·千克），平均稳态分布容积为2.88±1.81 L/千克，平均终末半衰期为4.29±2.29小时。皮下给药后，rIFN-β1a的吸收延长，血清浓度一般低于100 IU/mL。每日皮下注射8次后，未观察到rIFN-β1a在血清中的蓄积。相比之下，血清新蝶呤水平在静脉给药后12小时和皮下给药后24小时才升高至基线水平以上。静脉注射后24小时血清新蝶呤的平均升高幅度显著大于皮下给药后24小时。
