ABSORPTION AND IN-VIVO DISSOLUTION OF HYDROXYCHOLOROQUINE IN FED SUBJECTS ASSESSED USING DECONVOLUTION TECHNIQUES

1 Nine healthy subjects each received three doses of 155 mg rac-hydrox ychloroquine, as a tablet, an oral solution and by intravenous infusio n, in a randomised cross-over design study, 30 min after a standard hi gh fat breakfast. 2 Four methods of deconvolution were used to assess the absolute bioavailability of the tablet and oral solution doses. Th ese were the delta function method, the staircase approximation method , and two least squares methods using a single first-order input and a sequential first-order input. The mean (+/- s.d.) fraction absorbed e stimated by the four methods was 0.64 +/- 0.14 after the tablet and 0. 87 +/- 0.30 after the oral solution. Wide intersubject variability was observed (0. 50-0.91 for the tablet; 0.30-1.37 for the solution). 3 T he mean (+/- s.d.) absorption half-life was 3.7 +/- 2.0 h for the tabl et and 3.3 +/- 1.6 h for the solution, suggesting that absorption foll owing the tablet dose was not rate-limited by dissolution. 4 The in vi vo dissolution rate, extent of release and lag-time were determined us ing cube-root law and first-order input functions. Dissolution was fou nd to be rapid, after a significant lag-time, but incomplete in some s ubjects. 5 The rate and extent of absorption was similar to that repor ted previously for fasted subjects. The lag-time before absorption com menced in fed subjects (1.65 +/- 0.46 h) showed a significant three-fo ld increase over that reported previously in fasting subjects (0.63 +/ - 0.33 h), but this difference is not likely to be of clinical signifi cance.