title: Monoclonal antibodies: pharmacokinetics as a basis for new dosage regimens?
abstract: Complete monoclonal IgG antibodies which are in use in clinical practice share some pharmacological properties resulting in high concentrations in plasma. This fact is reflected in their low volumes of distribution, which can also be correlated with a high molecular weight and water solubility. This feature allows a novel approach to be applied to the dosing schedule for this group of drugs with fixed doses being used instead of the initially developed weight- or body surface-adjusted dosing schedules. In addition, the development of a new formulation containing hyaluronidase allows a subcutaneous route of administration to be used, because hyaluronidase creates a space in the subcutaneous tissue that helps antibody absorption. This method requires higher doses, but has allowed testing the feasibility of administering a fixed dose, with no individual dose adjustments based on weight or body surface. Moreover, loading doses are not needed, because the first dose results, within 3 weeks, in minimum concentrations that are higher than effective concentrations.
authors.affiliation: Department of Clinical Pharmacology, Clínica Universidad de Navarra, Pamplona, Spain jrazanza@unav.es.
authors.forename: J-R
authors.initials: JR
authors.lastname: Azanza
authors.affiliation: Department of Clinical Pharmacology, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Sádaba
authors.affiliation: Department of Clinical Pharmacology, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Gómez-Guiu
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000737:chemistry*; D007074:Immunoglobulin G / Q000276:immunology*; D008970:Molecular Weight; D012995:Solubility; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D006821:Hyaluronoglucosaminidase
keywords: Monoclonal antibodies; dosage; hyaluronidase; pharmacokinetics; route of administration