Date of Award

2020

Degree Name

Masters of Medicine

Schools and Centres

Medicine

First Supervisor

Professor Deborah Marriott

Second Supervisor

Doctor Stephanie Reuter Lange

Abstract

Ribavirin is used in the treatment of respiratory paramyxovirus infection in lung transplant recipients; however, its pharmacokinetic profile in the transplant population is unknown despite the potential for alterations due to underlying pathology. Furthermore, the ability of current regimens to meet exposure targets has not been established. This study examined the pharmacokinetics of ribavirin in a lung transplant population from which current and alternate dosing regimens were assessed. Population pharmacokinetic modelling was conducted in NONMEM using concentrationtime data from 24 lung transplant recipients and 6 healthy volunteers. Monte Carlo simulation was used to assess the ability of dosing regimens to achieve pre-specified target concentrations. A three-compartment model with first order elimination most adequately described ribavirin concentration-time data, with creatinine clearance and patient type (i.e. lung transplant) identified as significant covariates in the model. Simulations indicate that current regimens achieve efficacious concentrations within 24 hours of treatment initiation that increase to supra-therapeutic levels over the treatment period. A regimen of 8 mg/kg q6h oral for 48 hours followed by 8 mg/kg q24h oral for the remainder of the treatment period was predicted to result in >90% of patients exhibiting concentrations within the defined target range throughout the entire treatment course. Additional work to formally establish of target therapeutic concentrations is required; however, this study provides a valuable first step in determining optimal ribavirin treatment regimens for paramyxovirus infections in the lung transplant population.

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