Hydroxychloroquine
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
70.1 kg.
The NextDose
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).
Hydroxychloroquine
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.
Concentrations
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%.