HIGH-DOSE METRONIDAZOLE - PHARMACOKINETICS AND BIOAVAILABILITY USING AN IV PREPARATION AND APPLICATION OF ITS USE AS A RADIOSENSITIZER

  • 1 January 1980
    • journal article
    • research article
    • Vol. 64  (10-1) , 1087-1095
Abstract
An an extension of studies on the clinical use of nitroimidazoles as radiosensitizers [for hypoxic tumor cells], single-dose pharmacokinetic studies of i.v. metronidazole (500 mg/100 ml vials) were performed in 8 consenting patients. Single doses of 0.5, 1.0, 1.5 and 2.0 g (0.29-1.21 g/m2) were administered i.v. by a 0-order infusion pump. Serial timed blood and urine samples were assayed for metronidazole and its 2 metabolites (acetic acid and ethoxy compounds) using a high-pressure liquid chromatographic assay. Open 2-compartment kinetic characteristics of metronidazole were computed from simultaneous plasma infusion and urine excretion-rate equations using a nonlinear least-squares regression analysis program (NONLIN). Means of the 4 kinetic parameters were as follows (h-1): K12, 1.18; K21, 0.86; K10, 0.22; and k''e, 0.46 .times. 10-4. Means of the apparent volumes of distribution were (liters/kilogram): Vc, 0.41; VB, 1.02; and Vss, 0.75. The mean (.+-. SD) for .alpha.-half-life was 1.2 .+-. 1.3 h; that for .beta.-half-life was 9.8 .+-. 5.9 h. Seven of the 8 patients received a 2nd identical dose orally 1 wk later; and the absolute bioavailability was estimated to approximate 100%. Unless the oral route is not feasible and if immediate high peak blood levels are not necessary, oral metronidazole is the preferred route of administration of metronidazole for its radiosensitizing effects.