Pharmacokinetics of Immunoglobulin Administered via Intravenous or Subcutaneous Routes

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This article reviews pharmacokinetic studies of IgG administration by intravenous and subcutaneous routes. Intravenous immunoglobulin pharmacokinetics have been studied during replacement therapy for primary and secondary immunodeficiencies and other special circumstances (eg, infection prophylaxis in neonates). Subcutaneous immunoglobulin pharmacokinetics have been studied only during replacement therapy for primary immunodeficiency. Published studies vary greatly with respect to the nature of the patients studied, dose regimens, sampling schedules, and pharmacokinetic models, making comparisons difficult. With either route of administration, there is large variation in individual IgG elimination rates. Periodic measurement of serum IgG concentration is critical to monitor the adequacy of replacement during therapy.

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Physiology of immunoglobulins

Important studies of immunoglobulin (Ig) synthesis and catabolism in humans in vivo were conducted in the 1960s. In particular, the work of Waldmann and colleagues3, 4 established the fundamental behaviors of various Ig isotypes under a variety of physiologic and pathologic conditions. To determine the rate of disappearance of Ig by protein catabolism, these authors injected volunteers with small amounts of radioactive Ig of various isotypes and examined the rate of decline of serum

Immunoglobulin G replacement therapy

IgG replacement therapy is indicated for primary or secondary immunodeficiencies with hypogammaglobulinemia or impaired specific antibody formation.1 Purified human IgG preparations have been formulated specifically for IM, SC, and IV administration. Preparations suitable for IM or IV use may be given SC;2 however, preparations intended for IM or SC use may not be given IV because of content of IgG aggregates that may lead to systemic reactions. Dose regimens have been determined empirically in

Pharmacokinetics of intravenous immunoglobulin

After administration of relatively large amounts of IVIG (0.1–2 g/kg body mass), the IgG concentration in serum immediately rises, falls rapidly in the first 1 to 7 days, and then falls more slowly thereafter. The initial rapid fall is associated with passage of IgG out of the vasculature into lymph and extracellular fluid compartments. The subsequent decline is mainly caused by catabolism while IgG in lymph and tissues slowly diffuses back into the circulation. Many studies of healthy

Pharmacokinetics of subcutaneous immunoglobulin

Ig administration via the SC route is fundamentally different from IV administration.2 The dose is absorbed slowly and redistributed slowly, whereas concentration-dependent catabolism is ongoing. It is impractical to administer SCIG by a dose regimen comparable to IVIG, because of the relatively limited amount that can be accommodated subcutaneously (approximately 5–30 mL per site, depending on size/body mass index), even when multiple sites are used. Although IVIG is usually administered every

Summary

IgG equilibrates between intra- and extravascular compartments, and its catabolism is controlled by a complex concentration-dependent endocytic mechanism mediated by FcRn. Studies using radioactive labeled IgG in healthy adults indicated an elimination half-life of approximately 23 days, with a lower value for IgG3 of 7 days. A two-compartment pharmacokinetic model fits the data in several studies of bolus IgG replacement therapy but is not universally applied in studies of IgG decay rates.

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