Di Girolamo Guillermo, Kauffman Marcelo A, González Eliseo, Papouchado Mariana, Ramírez Alejandra, Keller Guillermo, Carbonetto César, Dabsys Susana, Vidal Alejandro, Sterin-Prync Aída, Diez Roberto A
Facultad de Ciencias Médicas, Universidad Favaloro, Buenos Aires, Argentina.
Arzneimittelforschung. 2008;58(4):193-8. doi: 10.1055/s-0031-1296492.
Blastoferon, in the following referred to as the test product, is a pharmaceutical product of interferon beta la (CAS 220581-49-7) currently marketed as a biosimilar to the innovator Interferon beta la product (referred to as the reference product). Pharmacokinetics and pharmacodynamIcs assays are critically relevant to demonstrate similarity between biopharmaceuticals. The aims of the present study were to investigate the bioavailability (BA) of the test product (either absolute or relative to the innovator product) and to compare the extent of increase of neopterin concentration following administration of either product. Two studies were performed: initially, an absolute BA assay with i.v. and s.c. injection of test product to 12 healthy subjects. Second, a formal relative BA study with s.c. injections of 88 microg of both products to 24 healthy volunteers. Blood samples for pharmacokinetic and pharmacodynamic profiling were drawn at different intervals after injection. Interferon beta (IFNB) concentrations were determined by ELISA. In the absolute BA study, a single s.c. dose of 44 microg of the test product resulted in a median bioavailable fraction of 29%, a median T(max) of 4 h (4-6) and a C(max) of 3.69 (3.27-4.41) IU x ml(-1). In the relative BA study, values for the test product were: median T(max) of 3 h (2-18), C(max) of 5.39 (4.99-6.31) IU x ml(-1), AUC (0-72) of 142.86 (134.16-190.15) IU x h x ml(-1) and AUC(0-infinity) of 190.95 (174.23-303.13) IU x h x ml(-1). The corresponding values for the innovator product were: T(max) of 3 h (1-24), C(max) of 4.44 (4.12-5.40) IU x ml(-1), AUC(0-72) of 128.77 (121.18-170.92) IU x h x ml(-1) and AUC(0-affinity) of 192.61 (183.04-286.46) IU x h x ml(-1). The AUC(0-72) ratio was 111% (CI 90%: 106-116), the AUC(0-affinity) was 99% (CI 90%: 92-107) and the C(max) ratio was 121% (CI 90%: 112-131). IFNB1a increased neopterin levels in both studies. Both products induced side-effects commonly reported for IFN with no serious adverse events. This study presents pharmacokinetics parameters of the test product and demonstrates similar bioavailability of IFNB1a for both pharmaceutical products.
促卵泡生成素释放激素，以下简称受试产品，是一种β-1a干扰素（CAS 220581-49-7）的药品，目前作为创新型β-1a干扰素产品（简称参比产品）的生物类似药上市。药代动力学和药效学分析对于证明生物制药之间的相似性至关重要。本研究的目的是研究受试产品（绝对生物利用度或相对于创新型产品的相对生物利用度）的生物利用度，并比较两种产品给药后新蝶呤浓度升高的程度。进行了两项研究：首先，对12名健康受试者进行静脉注射和皮下注射受试产品的绝对生物利用度测定。其次，对24名健康志愿者进行皮下注射88微克两种产品的正式相对生物利用度研究。注射后在不同时间间隔采集血样进行药代动力学和药效学分析。通过酶联免疫吸附测定法测定β-干扰素（IFNB）浓度。在绝对生物利用度研究中，单次皮下注射44微克受试产品导致生物利用度中位数为29%，T(max)中位数为4小时（4-6），C(max)为3.69（3.27-4.41）IU/ml。在相对生物利用度研究中，受试产品的值为：T(max)中位数为3小时（2-18），C(max)为5.39（4.99-6.31）IU/ml，AUC(0-72)为142.86（134.16-190.15）IU·h/ml，AUC(0-∞)为190.95（174.23-303.13）IU·h/ml。参比产品的相应值为：T(max)为3小时（1-24），C(max)为4.44（4.12-5.40）IU/ml，AUC(0-72)为128.77（121.18-170.92）IU·h/ml，AUC(0-∞)为192.61（183.04-286.46）IU·h/ml。AUC(0-72)比值为111%（90%置信区间：106-116），AUC(0-∞)为99%（90%置信区间：92-107），C(max)比值为121%（90%置信区间：112-131）。在两项研究中，IFNB1a均使新蝶呤水平升高。两种产品均引发了干扰素常见的副作用，未出现严重不良事件。本研究给出了受试产品的药代动力学参数，并证明了两种药品中IFNB1a的生物利用度相似。
