Hydroxychloroquine relative bioavailability: within subject reproducibility.
Six healthy volunteers received hydroxychloroquine sulphate 200 mg orally on four occasions (three tablets, one solution). Maximum hydroxychloroquine blood concentration (Cmax; range 135-422 ng ml-1) and time to maximum (tmax; range 1.5-7.0 h) for the three tablet doses showed significant differences between subjects (P < 0.009; between subject coefficients of variation (CVs) 34% and 27%, respectively). There were no within subject differences in Cmax (P = 0.32; mean within subject CV 11%), Cmax corrected for weight (P = 0.28) or tmax (P = 0.35; mean within subject CV 16%). Truncated areas under the hydroxychloroquine blood concentration-time curve of the three tablets were different between (P = 0.0001) but not within subjects (P = 0.13). Again, between subject CV (38%) was more than three times the mean within subject CV (12%). Bioavailability was not limited by tablet formulation. The significant variability in relative bioavailability between but not within individuals indicated that individualising dosing to target concentrations associated with optimal outcomes may minimise variability in response.
Tett
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S
Clinical Pharmacology and Toxicology, St Vincent's Hospital, Darlinghurst, New South Wales, Australia.
Day
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R
Cutler
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D
D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000493:pharmacokinetics*; D008297:Male
D006886:Hydroxychloroquine