Studies of hydroxyurea administered by continuous infusion: toxicity, pharmacokinetics, and cell synchronization.
Hydroxyurea was administered by means of two schedules designed to provide continuous 72-hour exposure of tumor cells to therapeutic drug levels. Toxicity and pharmacokinetics were determined for both an oral pulse dose schedule (every 4 hours x 18 doses) and continuous intravenous (IV) infusion for 72 hours. The maximal tolerated dose (MTD) was 800 mg/m2 every 4 hours for the oral route and 3.0 mg/m2/min x 72 hours for IV infusion. Granulocytopenia was dose-limiting for both schedules and correlated well with plasma-HU levels. Serial sampling of normal bone marrow (10 patients) and tumor tissue (3 patients) showed a modest degree of synchronization induced by continuous IV infusion of hydroxyurea. Interindividual pharmacokinetic variations severely limit the usefulness of the oral pulse schedule as a potential means of synchronizing cells. Hydroxyurea administered by continuous IV infusion may be useful as a synchronizing agent in humans.
D000284:Administration, Oral; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D004334:Drug Administration Schedule; D006207:Half-Life; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D007263:Infusions, Parenteral; D008940:Mitotic Index; D009369:Neoplasms / Q000188:drug therapy*; D013921:Thrombocytopenia / Q000139:chemically induced; D013997:Time Factors
D006918:Hydroxyurea