[Collection: Department of Health and Human Services on experimental PCP treatment] Item: 3 of 18
9 p. ; 28 cm.View a full description of this collection.
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National Institute of Allergy and Infectious Diseases
0Backgrounder
Trimetrexate
Questions and Answers
1.What is trimetrexate?
Trimetrexate is an investigational drug synthesized and patented by
Warner-Lambert Company. The drug has been studied extensively in
cancer and now shows promise as a treatment for Pneumocystis carinii
pneumonia (PCP), the leading cause of death in patients with AIDS.
2. How does trimetrexate work?
Trimetrexate is an antifolate, which works by interfering with the body's
utilization of the group of vitamins called folates. Folates are essential
to metabolic processes in both Pneumocystis organisms and in human
cells.
When trimetrexate is taken up by Pneumocystis organisms it interferes
with critical enzymes. In the laboratory, scientists have found that
trimetrexate is approximately 1500 times more potent against Pneumocystis
carinii than trimethoprim, which is currently licensed to treat PCP in
combination with sulfamethoxazole.
3. How is trimetrexate given to AIDS patients?
The treatment involves trimetrexate in combination with leucovorin, a
form of the vitamin folinic acid. Leucovorin protects human cells from
the lethal effects of trimetrexate. However, because leucovorin is not
taken up by Pneumocystis organisms, the Pneumocystis organisms are not
protected from the lethal effects of trimetrexate.
Trimetrexate given in combination with leucovorin has been demonstrated
to be well tolerated in more than 100 AIDS patients with PCP. In
contrast, the two drugs now approved for treating PCP--trimethoprim-
sulfamethoxazole and pentamidine isethionate--often cause side effects
significant enough to result in discontinuation of treatment in 30-50
percent of patients.
4. What does the treatment regimen involve?
In current clinical studies, trimetrexate is given by vein (intravenously)
once a day for 21 days. Leucovorin is given 4 times a day for 24 days,
either by vein or as tablets taken by mouth.
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Department of Health and Human Services. [Collection: Department of Health and Human Services on experimental PCP treatment], collection, March 8, 1988; (https://texashistory.unt.edu/ark:/67531/metadc915769/m1/3/: accessed June 5, 2024), University of North Texas Libraries, The Portal to Texas History, https://texashistory.unt.edu; crediting UNT Libraries Special Collections.