ISSN:
1432-1041
Keywords:
methotrexate
;
renal clearance
;
nonlinear pharmacokinetics
;
methotrexate-RIA
;
patients
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Summary The pharmacokinetics of methotrexate have been assessed at two dose levels in six patients recciving the drug for treatment of malignant disease. Each patient received bolus intravenous doses of 25 mg and 100 mg given at least one week apart, the order of administration being random. Blood and urine were collected until 48 h for methotrexate analysis by radioimmunoassay and data analysed by a model-independent pharmacokinetic approach. In each patient area under the methotrexate serum concentration-time curve (o to ∞) increased out of proportion to the increase in methotrexate dose. This was reflected in a mean clearance value after the 100 mg dose of 31±16 (SD) ml · min−1 compared with a mean clearance of 62±19 ml · min−1 following injection of 25 mg methotrexate. Renal clearance of methotrexate was markedly lower following the 100 mg dose (18±6 ml · min−1) than after 25 mg (53±19 ml · min−1). Saturation of the proximal tubular organic acid transport system is the likely cause of methotrexate's capacity limited elimination.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00558450
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