Cletoquine oxalate (Desethylhydroxychloroquine oxalate) is a major active metabolite of Hydroxychloroquine. Cletoquine oxalate is produced in the liver by CYP2D6, CYP3A4, CYP3A5, and CYP2C8 isoenzymes. Cletoquine oxalate is also a Chloroquine derivative and has the ability to against the chikungunya virus (CHIKV). Cletoquine oxalate has antimalarial effects and has the potential for autoimmune diseases treatment[1][2].
Hydroxychloroquine (5 mg/kg intravenously) is administered to BALB/c mice for blood and tissue to determine the content of Cletoquine (Desethylhydroxychloroquine). The tissue to blood concentration ratio (Kp) is ≥1, indicating accumulation of Cletoquine in tissues. The Cletoquine Kp ratio for the various tissues are observed in the descending order of liver (114.3)>kidney (24.4)>spleen (19.3)>lungs (16.5)>heart (5.5)[3].
References:
[1]. Kumar M, et al. Molecular docking studies of chloroquine and its derivatives against P23pro-zbd domain of chikungunya virus: Implication in designing of novel therapeutic strategies. J Cell Biochem. 2019 Oct;120(10):18298-18308.
[2]. Charlier B, et al. Development of a novel ion-pairing HPLC-FL method for the separation and quantification of hydroxychloroquine and its metabolites in whole blood. Biomed Chromatogr. 2018 Aug;32(8):e4258.
[3]. Chhonker YS, et al. Simultaneous quantitation of hydroxychloroquine and its metabolites in mouse blood and tissues using LC-ESI-MS/MS: An application for pharmacokinetic studies. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Jan 1;1072:320-327.