Current drug metabolism · 2018
A Review on Clinical Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics of Natalizumab: A Humanized Anti-α4 Integrin Monoclonal Antibody.
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Li Hao, Shi Fang-Hong, Huang Shi-Ying, Zhang Shun-Guo, Chen Min-Ling
Аннотация
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.
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.