10-Hydroxyketotifen (WR621365)[1] is a biologically inactive metabolite of
ketotifen. [2][3][4] Despite the mainstream scientific consensus that 10-hydroxyketotifen is a biologically inactive compound, its pharmacological properties are not very well studied outside the context of ketotifen, therefore, 10-hydroxyketotifen may still possess biological activity similarly to
norketotifen, another metabolite of ketotifen.[1]
Ketotifen is an antihistamine medication which metabolizes to several compounds, including 10-hydroxyketotifen. Ketotifen, like other antihistamines,[5][6] is mainly metabolized by the
cytochrome P450 (CYP) enzymes, especially
CYP3A4[7][8] in the liver. The CYP enzymes are responsible for the
oxidation and
demethylation of ketotifen, producing the major metabolites
norketotifen and 10-hydroxyketotifen. Norketotifen is pharmacologically active and has a similar potency as ketotifen, while 10-hydroxyketotifen is inactive. The metabolites are then conjugated with
glucuronic acid or sulfate and excreted in the urine and feces.[9][10]
The definition and measurement of biological activity of drugs can be complex: biological activity is often defined in terms of the ability of a molecule to effect a change in a biological process, which can be quantified and measured in various ways; as such, even if 10-hydroxyketotifen is currently deemed inactive, it is possible that under certain conditions or within specific biological assays, some level of activity might be observed.[1][11]
References
^
abcdMilner E, Sousa J, Pybus B, Auschwitz J, Caridha D, Gardner S, et al. (2012). "Ketotifen is an antimalarial prodrug of norketotifen with blood schizonticidal and liver-stage efficacy". European Journal of Drug Metabolism and Pharmacokinetics. 37 (1): 17–22.
doi:
10.1007/s13318-012-0080-2.
PMID22314893.
^Julien-Larose C, Guerret M, Lavene D, Kiechel JR (1983). "Quantification of ketotifen and its metabolites in human plasma by gas chromatography mass spectrometry". Biological Mass Spectrometry. 10 (3): 136–142.
doi:
10.1002/bms.1200100307.
PMID6850066.
^Bersier PM, Szczepaniak W, Ren M (1992). "Direct Differential Pulse Polarographic and Adsorptive Stripping Voltammetric Assay of Ketotifen in Tablets". Archiv der Pharmazie. 325 (5): 253–259.
doi:
10.1002/ardp.19923250502.
^Li L, Liu R, Peng C, Chen X, Li J (July 2022). "Pharmacogenomics for the efficacy and side effects of antihistamines". Exp Dermatol. 31 (7): 993–1004.
doi:
10.1111/exd.14602.
PMID35538735.