HYDROXYCHLOROQUINE RELATIVE BIOAVAILABILITY - WITHIN-SUBJECT REPRODUCIBILITY

Six healthy volunteers received hydroxychloroquine sulphate 200 mg ora lly on four occasions (three tablets, one solution). Maximum hydroxych loroquine blood concentration (C-max; range 135-422 ng ml(-1)) and tim e to maximum (t(max); range 1.5-7.0 h) for the three tablet doses show ed significant differences between subjects (P<0.009; between subject coefficients of variation (CVs) 34% and 27%, respectively). There were no within subject differences in C-max (P=0.32; mean within subject C V 11%), C-max corrected for weight (P=0.28) or t(max) (P=0.35; mean wi thin subject CV 16%). Truncated areas under the hydroxychloroquine blo od concentration-time curve of the three tablets were different betwee n (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 indivi duals indicated that individualising dosing to target concentrations a ssociated with optimal outcomes may minimise variability in response.