High-dose metronidazole: pharmacokinetics and bioavailability using an iv preparation and application of its use as a radiosensitizer

Journal Article · Wed Oct 01 04:00:00 EDT 1980 · Cancer Treat. Rep.; (United States)

OSTI ID:5923210

Rabin, H R; Urtasun, R C; Partington, J; Koziol, D; Sharon, M; Walker, K

As an extension of studies on the clinical use of nitroimidazoles as radiosensitizers, single-dose pharmacokinetic studies of iv metronidazole (500 mg/100-ml vials) were performed in eight consenting patients. Single doses of 0.5, 1.0, 1.5, and 2.0 g (0.29 to 1.21 g/m2) were administered iv by a zero-order infusion pump. Serial timed blood and urine samples were assayed for metronidazole and its two metabolites (acetic acid and ethoxy compounds) using a high-pressure liquid chromatographic assay. Open two-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 four kinetic parameters were (h-1): k12, 1.18; k21, 0.86; k10, 0.22; and k'e, 0.46 x 10(-4). Means of the apparent volumes of distribution were (liters/kg): Vc, 0.41; VB, 1.02; and Vss, 0.75. The mean (+- SD) for alpha-half-life was 1.2 +- 1.3 hours, and that for beta-half-life was 9.8 +- 5.9 hours. Seven of the eight patients received a second identical dose orally 1 week 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.

• OSTI ID: 5923210
• Journal Information: Cancer Treat. Rep.; (United States), Journal Name: Cancer Treat. Rep.; (United States) Vol. 64:10-11; ISSN CTRRD
• Country of Publication: United States
• Language: English

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62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOLS
ANTINEOPLASTIC DRUGS
AZOLES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IMIDAZOLES
INJECTION
INTAKE
INTRAVENOUS INJECTION
KINETICS
METABOLISM
METABOLITES
METRONIDAZOLE
NITRO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATIENTS
PHARMACOLOGY
RADIATION EFFECTS
RADIOSENSITIVITY EFFECTS
RADIOSENSITIZERS
REACTION KINETICS