High-dose Methotrexate: Preliminary Evaluation of a Pharmacokinetic Approach

Overview

Journal Cancer Chemother Pharmacol

Specialty Oncology

Date 1979 Jan 1

PMID 527209

Citations 20

Authors

S Monjanel

J P Rigault

J P Cano

Y Carcassonne

R Favre

Affiliations

Soon will be listed here.

Abstract

Clinical pharmacologic studies have been carried out in patients with head and neck tumors following 36-h continuous infusions of high-dose MTX (1.5 g/m2). The results indicated considerable variation in the amount of MTX in the blood of individual patients. To control these variations, a modified protocol was set up to try to attain the same MTX blood level in all subjects. The protocol has a pharmacokinetic basis and involves determination of the MTX kinetics in each patient. The information thus obtained allows us to compute a 36-h infusion dose so that the MTX plasma levels never exceed a threshold beyond which there is a risk of toxicity to the host. The computation is validated by taking a blood sample 6 h after the beginning of the infusion. If the MTX concentration is higher than its expected value, the infusion rate can then be immediately reduced. Analytical methods that will allow such a computation, the results of the clinical application of this pharmacokinetic approach, and some implications of such a method are discussed.

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