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New Dosing Regimens for Amifostine: A Pilot Study to Compare the Relative Bioavailability of Oral and Subcutaneous Administration with Intravenous Infusion
Author(s) -
Bonner H. S.,
Shaw L. M.
Publication year - 2002
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912700222011201
Subject(s) - amifostine , bioavailability , dosing , pharmacology , pharmacokinetics , medicine , oral administration , active metabolite , area under the curve , route of administration , metabolite , drug , toxicity
A phase I clinical trial was conducted to assess the feasibility of a more convenient and safe dosing regime for the cytoprotective drug amifostine. Two alternative routes of administration, oral and subcutaneous (SQ), each with a dose of 500 mg, were compared to a 7.5‐minute intravenous (IV) infusion, with a dose of 200 mg/m 2 , in normal, healthy volunteers (N =12). Bioavailability of amifostine (parent drug) and its pharmacologically active metabolite, WR‐1065, was evaluated by comparing the area under the concentration‐time curve (AUC) derived from HPLC analysis of amifostine and both protein‐free and protein‐bound WR‐1065 in all three routes of administration. Results showed that SQ (but not oral) administration of amifostine could provide a more effective dosing regimen, in terms of both a reasonable AUC for the bound form of WR‐1065 and decreased toxicity, compared to IV delivery. These data suggest that the protein‐ bound form of WR‐1065 plays an important role in contributing to the bioavailability of this clinically useful cytoprotective drug.