Stereoselective disposition of hydroxychloroquine and its metabolite in rats

Chirality
Y WeiS K Khalil

Abstract

Racemic hydroxychloroquine-sulfate (HCQ-sulfate) was administered to rats orally. Groups of 9 male and 9 female rats received doses of 0, 8, 16, or 24 mg/kg/day for 6 weeks, followed by a reduction of the higher doses to 8 mg/kg/day for the duration of the study. Whole blood samples were collected at 0, 3, 6, 8, and 10 weeks, and eleven tissues were harvested after the tenth week. The concentrations and enantiomer ratios of the parent drug and three metabolites, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ), were determined. The highest concentration of HCQ was found in the intestinal smooth muscle, and the lowest in the brain and adipose tissue. The highest concentrations of the metabolites were found in the liver, adrenals, and lung tissue. The metabolism of HCQ in the rats was found to be stereoselective with R/S > 1 for the drug and < 1 for the metabolites. Gender-specific differences in the proportions of the drug and its metabolites and their enantiomers in blood and tissue were found. Varying dosages appeared to have only a temporary influence on blood concentrations and not to effect the enantiomer ratios in blood. Only a limited number of tissues exhibited significant d...Continue Reading

References

Dec 1, 1990·Baillière's Clinical Rheumatology·S TettR Day
Jun 1, 1989·British Journal of Clinical Pharmacology·S E TettK F Brown
Jul 1, 1965·Toxicology and Applied Pharmacology·E W McChesneyD J Sullivan
May 1, 1967·Toxicology and Applied Pharmacology·E W McChesneyR J Fabian
Jul 18, 1983·The American Journal of Medicine·E W McChesney
Mar 1, 1993·Clinical Pharmacokinetics·P Augustijns, N Verbeke

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Citations

Dec 17, 2003·Clinical Pharmacokinetics·Dion R Brocks, Reza Mehvar
Sep 8, 2015·Journal of the Neurological Sciences·Marcus W KochV Wee Yong
Mar 31, 2005·Journal of Pharmaceutical and Biomedical Analysis·Carmem Dickow Cardoso, Pierina Sueli Bonato
Feb 14, 2018·The Journal of Pharmacology and Experimental Therapeutics·Keagan P CollinsDaniel L Gustafson
Oct 11, 2020·Proceedings of the National Academy of Sciences of the United States of America·Suzanne J F KapteinLeen Delang
Nov 12, 2020·The Journal of Pharmacology and Experimental Therapeutics·Keagan P CollinsDaniel L Gustafson
Oct 1, 2021·Annals of Neurology·Marcus W KochLuanne M Metz
Nov 5, 2021·Nature Reviews. Neurology·Heather Y F Yong, V Wee Yong

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