Abstract
Aim:
To investigate the population pharmacokinetics of recombinant human tumor necrosis factor receptor-Fc fusion protein (rhTNFR-Fc) administered via subcutaneous (SC) injection in healthy Chinese volunteers and in Chinese patients with ankylosing spondylitis (AS).
Methods:
Thirty-two healthy volunteers were randomly assigned to receive a single SC injection of 12.5, 25, 37.5, or 50 mg of rhTNFR-Fc. Twenty male patients with moderate AS were randomly assigned to receive seven consecutive SC injections of rhTNFR-Fc at either 25 mg twice a week (BIW) or 50 mg once a week (QW). Population pharmacokinetic (PK) analysis was applied to obtain PK parameters of rhTNFR-Fc by the NONMEM method.
Results:
The data were best described by a one-compartment model with lag time. We found that gender had a significant effect on the apparent clearance (CL/F), with the male CL/F ratio being only 0.665 times the female ratio; the absorption coefficient (F) of multiple dosages of rhTNFR-Fc was only 0.674 times that of a single dosage. The outcome parameters were CL/F (female: 0.168 L/h, male: 0.110 L/h), the apparent volume of distribution (Vd/F: 15.5 L), the absorption rate constant (Ka) (single dosage: 0.0605 h−1, multiple dosage: 0.0408 h−1), and the lag time (Tlag: 1.03 h). The inter-individual variability in the CL/F, Vd/F, Ka, and Tlag were 33.3%, 42.7%, 55.6%, and 81.8%, respectively.
Conclusion:
Chinese females have a higher CL/F than Chinese males, and multiple dosings can significantly decrease the absorption of rhTNFR-Fc (SC). The population PK parameters of rhTNFR-Fc in healthy Chinese volunteers and patients with AS were similar to those reported for subjects in published American studies.
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Acknowledgements
This work was financially supported by Celgen Bio-Pharmaceutical Co Ltd (Shanghai, China). The authors would like to thank Prof Rui WANG for direction of the clinical work. We are also thankful to Prof Feng HUANG, Prof Ze-ling CAI, Mr Xiao-hu DENG, and Ms Chun-hua YANG from General Hospital of PLA for their technical assistance. Thanks to our families for their understanding and support in our study, work, and life.
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Fang, Y., Li, Lj., Wang, R. et al. Population pharmacokinetics of rhTNFR-Fc in healthy Chinese volunteers and in Chinese patients with Ankylosing spondylitis. Acta Pharmacol Sin 31, 1500–1507 (2010). https://doi.org/10.1038/aps.2010.113
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DOI: https://doi.org/10.1038/aps.2010.113
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