NextDose: A web-based Bayesian dose forecasting tool

Last updated 27 July 2021

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%.

 

Target Concentration

 

The target 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%).

Copyright All rights 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.