A Review on Clinical Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics of Natalizumab: A Humanized Anti-α4 Integrin Monoclonal Antibody

Title:A Review on Clinical Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics of Natalizumab: A Humanized Anti-α4 Integrin Monoclonal Antibody

Volume: 19 Issue: 14

Author(s): Hao Li, Fang-Hong Shi*, Shi-Ying Huang, Shun-Guo Zhang*Min-Ling Chen

Affiliation:

• Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127,China

• Department of Pharmacy, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127,China

Keywords: Natalizumab, pharmacokinetics, pharmacodynamics, pharmacogenomics, antibody, anti-α4 integrin.

Abstract: Background: Natalizumab (NAT), a humanized monoclonal antibody, binding in both α4β1 and α4β7 integrins, is approved for the treatment of Multiple Sclerosis (MS) and Crohn’s Disease (CD). This review highlights the detailed Pharmacokinetics (PK) and Pharmacodynamics (PD) information of NAT, with the Pharmacogenomics (PG) properties of NAT.

Methods: We undertake a systemic English-language search of Medline, EMBASE, Cochrane Library electronic databases to identify all potential studies with PK, PD or PG properties of NAT (up to October 2017).

Results: Five papers contain detailed pharmacokinetic parameters are included in this review. Body weight is the most important factor associated with NAT concentration. Greater PK similarity and PD comparability is observed following Subcutaneous (SC) administration than Intramuscular (IM) administration. Initial difference in PK measures was observed between SC and Intravenous (IV) administration. However, trough NAT serum concentrations are similar between SC and IV administration after repeated dosing. Antibodies against NAT result in a low serum NAT concentration and cause a loss of efficacy of NAT. Gln-152, Lys-201, and Lys-256 are the three important point mutation on the α4 residues that NAT binds to. Syndecan-1 gene is a potential candidate gene for personalized approach for NAT use in MS.

Conclusion: As MS is a disease that affects young women most and NAT can pass placental barrier before delivery and into breast milk, a proper risk-benefit analysis of NAT therapy in lactating women are still needed. The relationship between Single Nucleotide Polymorphisms (SNPs) and NAT treatment are still not clear.

Cite this article as:

Li Hao, Shi Fang-Hong*, Huang Shi-Ying, Zhang Shun-Guo*, Chen Min-Ling, A Review on Clinical Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics of Natalizumab: A Humanized Anti-α4 Integrin Monoclonal Antibody, Current Drug Metabolism 2018; 19 (14) . https://dx.doi.org/10.2174/1389200219666180427165841