The change in the serum Ig concentration after each administration was evaluated using the pairedt-test == 3

The change in the serum Ig concentration after each administration was evaluated using the pairedt-test == 3. pharmacokinetics of human IgG was significantly different between the obese and lean rats after both the IV and SC administration of 0.5 g/kg. Furthermore, a significant difference in endogenous rat IgG was observed between the two strains. In the human study, total serum IgG and subtype (IgG1, IgG2, IgG3, IgG4) half-life negatively correlated with the body mass index and fat mass. The mean change in the total serum IgG concentration was significantly correlated to body mass index and fat mass. The results of the studies corroborated one another. In the animal study, most pharmacokinetic parameters of human IgG following IV and SC administration were significantly affected by obesity and changes in the body composition. In the clinical study, the mean serum IgG change after the IVIG administration strongly correlated to the BMI and body fat mass. Future studies are needed to establish the outcomes achieved with more frequent dosing in obese individuals with primary immunodeficiency. Keywords:IVIG, primary immunodeficiency, immune globulin, body composition == 1. Introduction == Approximately 250,000 patients in the United States are diagnosed with primary immunodeficiency, and immune globulin G (IgG) replacement is the mainstay of therapy [1]. Current dosing practices for intravenous immune globulin (IVIG) may be inadequate for extreme body weight [2,3,4]. Actual, ideal, and adjusted (taking a portion of the excess body weight above ideal body weight, usually 40%, and adding to the ideal body weight) body weight-based dosing strategies are suggested in the literature [4,5,6]. These recommendations are based on expert opinion rather than high-quality evidence. Adopting a specific strategy for dosing is usually highly variable, depending on the clinician and institutional setting [5]. In the U.S., many payors have adopted strategies to reduce IgG therapy costs by capping doses. These recommendations are often based on the presumption that IgG distribution is limited to the vascular space [7]. While this assertion is usually logical, it does not account for the changes adipose tissue may confer on target sites nor for the adipose tissues potential to function as a metabolic sink or a source of inflammatory mediators [8]. The latter would be especially important in patients receiving SC immune globulin administration. Several observational studies have evaluated IgG dosing in obese patients [2,9,10,11], and are often cited to support dosing strategies. Many of these studies were not representative of the general population, contained a wide variety of patients with different IgG indications, DL-Menthol and had sparse serum sampling. Moreover, IgG distribution is not only a function of the partition coefficient, but may be DL-Menthol influenced by active transport and inflammation [8]. Using actual body weight for the dose calculations is the current recommendation in the FDA-approved prescribing information for IVIG products. Using actual body weight to dose IgG in obese patients may increase the risk of thrombosis, due to the increased blood viscosity, activation of platelets, or vasospasm [9,10]. Increased blood viscosity has been reported Efnb1 as IgG dose-dependent [9,12,13]. The use of ideal or adjusted body weights have been advocated to reduce the side effects and drug expenditures [2]. The impact of using measures of body weight other than the actual body weight to calculate IgG doses on clinical outcomes and the effect of obesity on IgG pharmacokinetics has not been experimentally evaluated. Although some data suggest actual body weight for IgG dosing, in a survey (2015) of 92 academic institutions in the United States, approximately 60% of respondents indicated they do not use the actual body weight to dose IgG [5]. This choice is likely related to the cost of IgG treatment, which tremendously impacts the healthcare system. The cost of IVIG therapy for patients with primary immunodeficiency is usually approximately $30,000 per patient annually [14], which corresponds to a total of more than $3.5 billion/per year for primary immunodeficiency alone (there are more than 150 unlabeled uses for IgG reported in the literature) [15]. Using the ideal or adjusted body weight for dosing may conserve IgG [16]. To this end, the doses are frequently rounded to the nearest vial size [17]. The mechanisms by which obesity affects the pharmacokinetics of protein therapeutics, including IgG, DL-Menthol have not been sufficiently investigated. It was recently suggested that IgG should be dosed based on.