Methods and compositions for inhibiting uridine secretion
AssigneeThe UAB Research Foundation
InventorsJean-Pierre Sommadossi, Mahmoud H. el Kouni
Life of this patent
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Abstract
Methods and pharmaceutical compositions effective to increase intracellular and plasma uridine concentrations are disclosed. Certain compositions and methods of using such compositions have been found to be effective to inhibit uridine secretion in a subject, thus increasing uridine concentration. Treatments that increase uridine concentrations are useful to combat many treatments and can also be effective in protecting or rescuing uninfected and normal cells that are subject to toxic side effects induced by the administration of certain chemotherapeutic compounds.
Claims13
A method for protecting and/or rescuing normal or uninfected cells from toxicity resulting from the administration of a chemotherapeutic agent to a patient comprising:
- (a) administering an anticancer agent selected from the group consisting of a pyrimidine base and a pyrimidine nucleoside analogue;
- and
- (b) administering an amount of a uridine secretion inhibiting compound effective to increase plasma and intracellular uridine levels, the uridine secretion inhibiting compound being represented by compounds having the following formula and pharmaceutically acceptable salts thereof:
- ##STR7## where:
- R.sub.1 and R.sub.3 are lower alkoxy groups having from 1 to 3 carbon atoms, and are the same or different, n is an integer from 1 to 3, m is 2 or 3, R.sub.2 is ##STR8## where R.sub.4 and R.sub.6 are methyl, ethyl or propyl, and are the same or different, and R.sub.5 is methyl, ethyl, propyl or butyl;
- or where R.sub.2 is ##STR9## where x is an integer from 2 to 4 and y is 2 or 3, and the sum of x and y is from 5 to 7.
A method for protecting and/or rescuing normal or uninfected cells from toxicity resulting from the administration of a chemotherapeutic agent to a patient comprising administering to the patient:
- (a) 5-fluorouracil;
- and
- (b) an amount of a uridine secretion inhibiting compound effective to increase plasma and intracellular uridine levels, the uridine secretion inhibiting compound being represented by compounds having the following formula and pharmaceutically acceptable salts thereof:
- ##STR10## where:
- R.sub.1 and R.sub.3 are lower alkoxy groups having from 1 to 3 carbon atoms, and may be the same or different, n is an integer from 1 to 3, m is 2 or 3, R.sub.2 is ##STR11## where R.sub.4 and R.sub.6 are methyl, ethyl or propyl, and may be the same or different, and R.sub.5 is methyl, ethyl, propyl or butyl;
- or where R.sub.2 is ##STR12## where x is an integer from 2 to 4 and y is 2 or 3, and the sum of x and y is from 5 to 7.
A method for protecting and/or rescuing normal or uninfected cells from toxicity resulting from the administration of a chemotherapeutic agent to a patient comprising administering to the patient an anticancer agent selected from the group consisting of a pyrimidine base and a pyrimidine nucleoside analogue, and a uridine secretion inhibiting compound that competes with uridine in the renal transport mechanism of uridine and is selected from the group consisting of L-uridine, L-2,3'-dideoxyuridine, and D-2',3'-dideoxyuridine in an amount effective to increase intracellular and plasma uridine levels.
Dependencies are inferred from the claim text.