NextDose: A web-based Bayesian dose
Last updated 27 July 2021
A population PK analysis
of hydroxychloroquine obtained in groups of healthy subjects and patients with
rheumatoid disease was published in 2003 (Carmichael, Charles et al. 2003). The model describes input with
first-order absorption and a lag time. Distribution is to a single compartment
with first-order elimination. The average weight of subjects and patients was
model accounts for differences in body size using theory based allometry. It
also accounts for maturation of clearance in neonates and infants using the
maturation function described for glomerular filtration rate (Rhodin, Anderson et al. 2009).
is thought to be partly metabolized and partly eliminated renally. The model
used in NextDose assumes 40% of clearance is renal and the change in renal
clearance is predictable from renal function predicted using creatinine
clearance. The total clearance will be the same as that reported by Carmichael
et al. when renal function is 1.
were measured in whole blood so it can be expected that the measured value will
vary with haematocrit. To account for any difference in haematocrit from the
standard value of 45% the haematocrit may be entered as an observation.
Predicted concentrations will be adjusted for the observed haematocrit. Dose
predictions will be based on whole blood concentrations at a standard
haematocrit of 45%.
concentration for hydroxychloroquine has not been clearly established. The
average steady state concentration in patients with rheumatoid arthritis taking
400 mg hydroxychloroquine sulphate was 0.98 mg/L (Carmichael, Charles et al. 2003). A whole blood target
concentration of 1 mg/L is suggested (haematocrit 45%).
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reserved | Developed by Sam Holford & Nick Holford 2012-2021
Carmichael, S. J., B. Charles and S.
E. Tett (2003). "Population pharmacokinetics of hydroxychloroquine in
patients with rheumatoid arthritis." Ther Drug Monit 25(6): 671-681.
Rhodin, M. M., B. J. Anderson, A. M. Peters, M. G.
Coulthard, B. Wilkins, M. Cole, E. Chatelut, A. Grubb, G. J. Veal, M. J. Keir
and N. H. Holford (2009). "Human renal function maturation: a quantitative
description using weight and postmenstrual age." Pediatr Nephrol 24(1): 67-76.