1. Field of the Invention
The invention relates to novel aldehyde adducts of triamterene, to pharmaceutical compositions containing said adducts and to methods of administering same to mammals to elicit a diuretic response therein without substantial loss of potassium.
2. Description of the Prior Art
Triamterene, also known as 2,4,7-triamino-6-phenylpteridine, is a well-known pteridine diuretic having the structural formula: ##STR1## The diuretic, hypotensive and potassium-saving properties of triamterene, when used alone or in combination with other diuretics, has been known for some time. (See, for example, Weinstock et al U.S. Pat. No. 3,081,230, hereby incorporated by reference herein in its entirety and relied upon.) Triamterene is currently marketed as DYRENIUM.RTM., in which it is the sole active ingredient, and in a combination with hydrochlorothiazide available under the name DYAZIDE.RTM.. The drug is widely used, particularly for its ability to restrict the loss of potassium caused by other diuretics. Unfortunately, as has been shown previously, e.g., Clin. Pharmacol. & Ther. 21, 610 (1977), the plasma and the urine concentration of triamterene following the recommended clinical dose is extremely low, due to incomplete absorption. The bioavailability of the drug, based on the urinary concentration of the drug and its metabolite, has been found to vary between 30% and 70%. The low aqueous solubility of this compound, i.e., 45 .mu.g/ml, as reported in J. Pharm. Sci. 53, 1325 (1964), as well as its limited solubility in lipid-like solvents, is primarily responsible for its impaired dissolution in vivo, and hence, its complete absorption. Accordingly, a clear need exists for a means of effectively increasing the solubility, and hence the bioavailability, of triamterene.
USPTO Backgrounds
USPTO Backgrounds