Compositions and methods of enhancing 5-hydroxytryptophan bioavailability

Abstract

Provided are methods of enhancing bioavailability of enterally administered 5-hydroxytryptophan (5-HTP) in a subject in need thereof, said method comprising enterally co-administering low-dose carbidopa with said 5-HTP, as well as pharmaceutical formulations useful for the same. In some embodiments, the 5-HTP and / or low-dose carbidopa are provided as slow-release formulation(s).

Description

[0001] Statement of Government Support [0002] This invention was made with government support under Federal Grant 2R01MH079201-06A1 awarded by the National Institutes of Health (NIH). The government has certain rights in this invention. Background technique [0003] 5-Hydroxytryptophan (5-HTP) is the natural direct precursor of 5-hydroxytryptamine (aka, 5-hydroxytryptamine, 5-HT). 5-HTP has been reported to have therapeutic potential in a range of diseases related to central nervous system function (Turner et al., 2006a), but exhibits rapid absorption in humans (T Max ~1h) and rapid elimination (T 1 / 2 ~2h) (Gijsman et al., 2002; Westenberg et al., 1982). 5-HTP alone as a molecule may not be suitable for drug therapy because of the rapid occurrence after administration associated with C Max associated adverse events, and requiring doses of 4-6 times per day to maintain reasonably stable 5-HTP exposure, such dosage requirements are unrealistic and impractical in the genera...

AI Technical Summary

Problems solved by technology

5-HTP alone as a molecule may not be suitable for drug therapy because of the rapid occurrence after administration associated with C Max associated adverse events, and require doses of 4-6 times per day to maintain reasonably stable 5-HTP exposure, a dosage requirement that is unrealistic and impractical in the general therapeutic setting (Jacobsen et al, 2016a)

Furthermore, in humans, congenital amino acid decarboxylase deficiency causes severe autonomic, motor, and other symptoms, suggesting that long-term PDI treatment may have broad-spectrum toxic effects (Manegold et al., 2009)

[0009] Overall, the long-term safety of PDI treatment without levodopa in otherwise healthy individuals has not been established, and the pharmacology of PDI may negatively affect various physiological systems in the periphery

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