7-Hydroxymethotrexate as a urinary metabolite in human subjects and rhesus monkeys receiving high dose methotrexate
Human subjects and rhesus monkeys receiving the antitumor agent methotrexate at the high dose levels recently introduced into clinical use (greater than 50 mg/kg) excrete significant amounts of the metabolite 7-hydroxymethotrexate. The metabolite is not detected in these species after methotrexate t...
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| Published in | The Journal of clinical investigation Vol. 57; no. 2; pp. 534 - 538 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
01.02.1976
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0021-9738 |
| DOI | 10.1172/JCI108308 |
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| Abstract | Human subjects and rhesus monkeys receiving the antitumor agent methotrexate at the high dose levels recently introduced into clinical use (greater than 50 mg/kg) excrete significant amounts of the metabolite 7-hydroxymethotrexate. The metabolite is not detected in these species after methotrexate therapy at conventional dose levels. The evidence indicates that in primates, the in vivo conversion of methotrexate to 7-hydroxymethotrexate is a dose-dependent phenomenon, with the enzyme system(s) catalyzing the reaction having a low affinity for the drug. |
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| AbstractList | Human subjects and rhesus monkeys receiving the antitumor agent methotrexate at the high dose levels recently introduced into clinical use (greater than 50 mg/kg) excrete significant amounts of the metabolite 7-hydroxymethotrexate. The metabolite is not detected in these species after methotrexate therapy at conventional dose levels. The evidence indicates that in primates, the in vivo conversion of methotrexate to 7-hydroxymethotrexate is a dose-dependent phenomenon, with the enzyme system(s) catalyzing the reaction having a low affinity for the drug. Human subjects and rhesus monkeys receiving the antitumor agent methotrexate at the high dose levels recently introduced into clinical use (greater than 50 mg/kg) excrete significant amounts of the metabolite 7-hydroxymethotrexate. The metabolite is not detected in these species after methotrexate therapy at conventional dose levels. The evidence indicates that in primates, the in vivo conversion of methotrexate to 7-hydroxymethotrexate is a dose-dependent phenomenon, with the enzyme system(s) catalyzing the reaction having a low affinity for the drug.Human subjects and rhesus monkeys receiving the antitumor agent methotrexate at the high dose levels recently introduced into clinical use (greater than 50 mg/kg) excrete significant amounts of the metabolite 7-hydroxymethotrexate. The metabolite is not detected in these species after methotrexate therapy at conventional dose levels. The evidence indicates that in primates, the in vivo conversion of methotrexate to 7-hydroxymethotrexate is a dose-dependent phenomenon, with the enzyme system(s) catalyzing the reaction having a low affinity for the drug. |
| Author | Jacobs, S A Johns, D G Stoller, R G Chabner, B A |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/1062383$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | Adult Animals Bone Neoplasms - drug therapy Carcinoma, Squamous Cell - drug therapy Child Female Histocytochemistry Humans Kidney - metabolism Lung Neoplasms - drug therapy Macaca mulatta Male Methotrexate - administration & dosage Methotrexate - analogs & derivatives Methotrexate - metabolism Methotrexate - therapeutic use Methotrexate - urine Middle Aged Osteosarcoma - drug therapy Time Factors |
| Title | 7-Hydroxymethotrexate as a urinary metabolite in human subjects and rhesus monkeys receiving high dose methotrexate |
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