Population pharmacokinetics of rhTNFR-Fc in Chinese patients with rheumatic arthritis.

OBJECTIVE: We aimed to investigate the population pharmacokinetics (PK) of soluble recombinant human tumor necrosis factor receptor fusion protein (rhTNFR- Fc) in Chinese patients with rheumatic arthritis (RA). The PK differences between Chinese patients with RA and healthy Chinese subjects were also compared. METHODS: 40 patients were randomized to a single subcutaneous (SC) injections of 12.5 mg (n = 10), 25 mg (n = 10), and 50 mg (n = 10) of rhTNFR-Fc, and six SC injection of rhTNFR- Fc at 25 mg once in 3 days (n = 10) respectively. A total of 550 serum concentration data points were collected in the RA patients. The population PK analysis was performed by NONMEM. Based on the population PK parameters obtained herein and those reported in healthy Chinese subjects, simulation was conducted to compare the difference of rhTNFR-Fc exposure between these populations. RESULTS: The PK data of Chinese patients with RA were best described by a one compartment model with lag time. A higher CL/F was noted in RA patients compared with that of the healthy Chinese subjects (1.64 L/h vs. 1.10 L/h), and a lower Ka was noticed in the RA patients compared with that of the healthy subjects (0.0317 h-1 vs. 0.0605 h-1). The simulate results showed that rhTNFR-Fc exposure in Chinese patients with RA was significantly lower than that in healthy subjects. The mean patients/healthy subjects C(max) and AUC(ss) ratios were 0.870 and 0.890, respectively. CONCLUSIONS: A population PK model of rhTNFR- Fc was developed in Chinese patients with RA. Statistical difference was noted in the PK of rhTNFR-Fc between Chinese patients with RA and healthy Chinese subjects.