The identifiability of a turnover model for allopurinol urate-lowering effect-

Introduction. Allopurinol is used for the treatment of gout. The primary physiological response to allopurinol therapy is a reduction in serum urate concentrations. Attempts to model the pharmacokinetics and pharmacodynamics (PK & PD) of allopurinol using a turnover model have consistently produced unstable models with imprecise and biased estimates for some PD parameters (e.g. Kout) […]

What is the best dosing regimen for allopurinol in patients with renal impairment?

Aims To develop a population PKPD model for plasma allopurinol, oxypurinol and serum urate To investigate the best regimen for dosing allopurinol in patients with renal impairment Methods The data were sourced from four studies (one unpublished).1-3 The population analysis was conducted using NONMEM® v.7.2. Covariates analysed included creatinine clearance (as predicted from the Cockcroft-Gault […]

The use of PKPD simulations to inform the rational use of medicines in clinical practice: the case of simvastatin circadian dosing

Background: The overarching motivation for this research is the belief that simulations from a pharmacokinetic-pharmacodynamic (PKPD) model provide an opportunity to explore the rational use of medicines in clinical practice. The current practice of dosing simvastatin in the evening rather than the morning is presented as a motivating example. This regimen is based largely on […]

Optimal designs for warfarin INR monitoring

Background: Warfarin is used to treat and prevent blood clots. It is one of the most difficult drugs to dose accurately, with daily maintenance doses varying by more than tenfold between patients. Evidence from pharmacogenetic studies indicates the importance of CYP2C9 and VKORC1 polymorphisms in predicting warfarin dose variability. However, this information   is of limited value […]