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Kinetics of metoprine, a lipid-soluble antifolate.
- Source :
- British Journal of Clinical Pharmacology; 1981, Vol. 12 Issue 5, p675-680, 6p
- Publication Year :
- 1981
-
Abstract
- 1 Using a dihydrofolate reductase inhibition assay, we have conducted either pharmacokinetic studies in six patients receiving metoprine. 2 The serum level v time-curve for metoprine equivalents was irregular; first-order elimination was not observed during the study period of 0- 120 h. A model-independent analysis was therefore performed, employing the area under the curve during the first 120 h (AUC). 3 At an oral dose of 65 mg/m2 without leucovorin, a peak level of 0.6 microgram/ml and an AUC of 52 micrograms ml-1 h produced significant leukopenia and thrombocytopenia. 4 At doses ranging from 100 mg/m2 to 175 mg/m2 orally, with leucovorin administration 40 mg/m2 intravenously at 24 and 96 h, haematologic toxicity was seen in only 1 patient who received 175 mg/m2. This patient also had the highest peak serum level (2.8 micrograms/ml) and AUC (228 micrograms ml-1 h). 5 One partial response and one minor regression were observed in the studied patients; these two patients had the 175 mg/m2 dose, highest peak levels (2.4 and 2.8 micrograms/ml) and highest AUCs (197 and 228 micrograms ml-1 h). The other patients had lower peak levels and AUCs and had neither therapeutic response nor hematologic toxicity. 6 The AUC and peak serum levels were linearly related to each other (P less than 0.001). 7 Total urinary excretion of dihydrofolate reductase inhibitors (as metoprine equivalents) in the first 120 h ranged from 5 to 17% of the administered dose. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03065251
- Volume :
- 12
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- British Journal of Clinical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 90924248
- Full Text :
- https://doi.org/10.1111/j.1365-2125.1981.tb01288.x