Bioavailability of Hydroxychloroquine Tablets Assessed with Deconvolution Techniques

Abstract

Four deconvolution methods (staircase, delta function, and least squares methods using single and sequential first-order input functions) were used to assess the absolute bioavailability of hydroxychloroquine tablets in nine healthy fasting volunteers. The volunteers received, in a random crossover design, a 155-mg oral tablet and a 155-mg iv infusion of racemic hydroxychloroquine. The mean fractions of the dose absorbed, calculated using the four deconvolution methods, were not statistically different (p = 0.70). The mean fraction absorbed (±SD) was 0.67 ± 0.12, which was not significantly different from that reported previously in a conventional bioavailability study (p = 0.22). The mean absorption half-life was calculated to be 4.0 ± 1.3h. The mean lag time before absorption commenced was 0.57 ± 0.30h. The fraction of the dose absorbed ranged from 0.44 to 0.86. Low and/or variable bioavailability of hydroxychloroquine may be a cause of therapeutic failure in some patients. Validation of the deconvolution methods means that these techniques may now be used to assess the bioavailability of hydroxychloroquine in patients. An advantage of these methods is that samples need only be collected over the expected time period of absorption, rather than the whole time drug can be detected in the body, as is required in conventional area under the concentration-time curve ratio methods. Deconvolution studies may be completed in 2 weeks rather than the 10 months required for a conventional bioavailability study of hydroxychloroquine.