Population pharmacokinetic modelling of intravenous immunoglobulin in patients with predominantly antibody deficiencies. 2021

Jian Lynn Lee, and Shamin Mohd Saffian, and Mohd Makmor-Bakry, and Farida Islahudin, and Hamidah Alias, and Lokman Mohd Noh, and Intan Hakimah Ismail, and Noraida Mohamed Shah
Centre for Quality Management of Medicines, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.

There is considerable interpatient variability in the pharmacokinetics (PK) of intravenous immunoglobulin G (IVIG), causing difficulty in optimizing individual dosage regimen. This study aims to estimate the population PK parameters of IVIG and to investigate the impact of genetic polymorphism of the FcRn gene and clinical variability on the PK of IVIG in patients with predominantly antibody deficiencies. Patients were recruited from four hospitals. Clinical data were recorded and blood samples were taken for PK and genetic studies. Population PK parameters were estimated by nonlinear mixed-effects modelling in Monolix®. Models were evaluated using the difference in objective function value, goodness-of-fit plots, visual predictive check and bootstrap analysis. Monte Carlo simulation was conducted to evaluate different dosing regimens for IVIG. A total of 30 blood samples were analysed from 10 patients. The immunoglobulin G concentration data were best described by a one-compartment model with linear elimination. The final model included both volume of distribution (Vd) and clearance (CL) based on patient's individual weight. Goodness-of-fit plots indicated that the model fit the data adequately, with minor model mis-specification. Genetic polymorphism of the FcRn gene and the presence of bronchiectasis did not affect the PK of IVIG. Simulation showed that 3-4-weekly dosing intervals were sufficient to maintain IgG levels of 5 g L-1 , with more frequent intervals needed to achieve higher trough levels. Body weight significantly affects the PK parameters of IVIG. Genetic and other clinical factors investigated did not affect the disposition of IVIG.

UI MeSH Term Description Entries
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009010 Monte Carlo Method In statistics, a technique for numerically approximating the solution of a mathematical problem by studying the distribution of some random variable, often generated by a computer. The name alludes to the randomness characteristic of the games of chance played at the gambling casinos in Monte Carlo. (From Random House Unabridged Dictionary, 2d ed, 1993) Method, Monte Carlo
D003198 Computer Simulation Computer-based representation of physical systems and phenomena such as chemical processes. Computational Modeling,Computational Modelling,Computer Models,In silico Modeling,In silico Models,In silico Simulation,Models, Computer,Computerized Models,Computer Model,Computer Simulations,Computerized Model,In silico Model,Model, Computer,Model, Computerized,Model, In silico,Modeling, Computational,Modeling, In silico,Modelling, Computational,Simulation, Computer,Simulation, In silico,Simulations, Computer
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D016756 Immunoglobulins, Intravenous Immunoglobulin preparations used in intravenous infusion, containing primarily IMMUNOGLOBULIN G. They are used to treat a variety of diseases associated with decreased or abnormal immunoglobulin levels including pediatric AIDS; primary HYPERGAMMAGLOBULINEMIA; SCID; CYTOMEGALOVIRUS infections in transplant recipients, LYMPHOCYTIC LEUKEMIA, CHRONIC; Kawasaki syndrome, infection in neonates, and IDIOPATHIC THROMBOCYTOPENIC PURPURA. Antibodies, Intravenous,Human Intravenous Immunoglobulin,IV Immunoglobulin,IVIG,Intravenous Antibodies,Intravenous Immunoglobulin,Intravenous Immunoglobulins,Alphaglobin,Endobulin,Flebogamma DIF,Gamimmune,Gamimmune N,Gamimune,Gamimune N,Gammagard,Gammonativ,Gamunex,Globulin-N,IV Immunoglobulins,Immune Globulin Intravenous (Human),Immune Globulin, Intravenous,Immunoglobulins, Intravenous, Human,Intraglobin,Intraglobin F,Intravenous IG,Intravenous Immunoglobulins, Human,Iveegam,Modified Immune Globulin (Anti-Echovirus Antibody),Privigen,Sandoglobulin,Venimmune,Venoglobulin,Venoglobulin-I,Globulin N,Human Intravenous Immunoglobulins,Immunoglobulin, Human Intravenous,Immunoglobulin, IV,Immunoglobulin, Intravenous,Immunoglobulins, Human Intravenous,Immunoglobulins, IV,Intravenous Immune Globulin,Intravenous Immunoglobulin, Human,Venoglobulin I
D061605 Administration, Intravenous Delivery of substances through VENIPUNCTURE into the VEINS. Intravenous Administration,Administrations, Intravenous,Intravenous Administrations

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