SYMPOSIUM 13: Improving dosing for renally eliminated medicines
Tracks
Track 1
| Tuesday, September 23, 2025 |
| 3:30 PM - 5:00 PM |
| Grand Copthorne Waterfront Hotel - Grand Ballroom I |
Details
Renal elimination is a major pathway for drug clearance across many medication classes, including antibiotics. Failing to adequately predict differences in renal function can lead to suboptimal concentrations and therapy failure, or toxicity. Immaturity of organs in neonates and babies, renal dysfunction and dialysis procedures can have significant impacts on drug clearance and therefore on dose. Models that can account for these factors can be used to improve dosing for the individual. This symposium explores methods of predicting renal function for improved dosing, with a focus on antibiotics.
Speaker
Dr Conor O'Hanlon
University of Auckland, Pharmaceutical Research and Early Development, F. Hoffmann-La Roche AG, Basel
How to predict renal function from premature neonates to adults
Biography
Prof Nick Holford
Director
University Of Auckland
A physiological approach to renal clearance informed by renal function
Biography
Professor Holford obtained his medical qualifications (MBChB, MRCP) in the United Kingdom. In 1983 he moved to Auckland, New Zealand to join the University of Auckland in the Dept of Pharmacology & Clinical Pharmacology. Until 1989 he had a part time appointment as a Specialist in Internal Medicine at Auckland Hospital. During this period he was elected Fellow of the Royal Australasian College of Physicians. He retired from the University of Auckland as Professor Emeritus of Clinical Pharmacology at the end of 2021. His interests are in applying pharmacokinetics and pharmacodynamics to clinical pharmacology and developing tools to aid dose individualization (www.nextdose.org).
Dr Laila Nassar
Rambam Medical Censer, Haifa
Pharmacokinetics during haemodialysis and hemodiafiltration, application to amikacin
Biography
Dominika Fuhs
Monash University
Disposition of colistin in critically ill patients on sustained low-efficiency dialysis: a population pharmacokinetic study and Monte Carlo simulations
Abstract
Colistin (administered as the inactive prodrug colistin methanesulphonate [CMS]) is often used to treat infections in critically-ill patients undergoing sustained low-efficiency dialysis (SLED).
We aimed to develop a population pharmacokinetic (popPK) model for colistin in patients undergoing SLED, and evaluate the probabilities of antibacterial benefit and colistin nephrotoxicity for different dosing regimens via simulations.
A prospective popPK study included 13 critically-ill patients treated with CMS and receiving SLED (6-8h) for renal support. The PK of formed colistin was studied on both a nonSLED and a SLED day. Colistin plasma concentrations were analysed using the popPK approach. Monte Carlo simulations (MCS) for dosing regimen evaluation were performed.
A linear one-compartment PK disposition model best described the data. The total body clearance of colistin (excluding SLED clearance) was 1.69L (21%) [population mean (between subject variability)] with 42% interoccasion variability. Colistin clearance during the SLED period was estimated to be 3.49L (42%). We evaluated the probability of target attainment defined as percentage of patients achieving relevant average colistin plasma concentration (Cavg) targets: >80% for Cavg ≥2 mg/L, >90% for Cavg ≥1.5 mg/L and <30% for Cavg ≥4 mg/L for the first 24h of therapy initiation on a SLED or nonSLED day as well as maintenance therapy.
Colistin clearance was substantially higher during SLED; therefore, SLED should be accounted for in CMS dosing regimens. This analysis provides comprehensive information regarding the achievement of clinically desirable average plasma colistin concentrations (including evaluation of loading doses) for two dosing regimens and six different SLED administration scenarios.
Key words:
Population pharmacokinetic modelling, colistin, sustained low-efficiency dialysis
We aimed to develop a population pharmacokinetic (popPK) model for colistin in patients undergoing SLED, and evaluate the probabilities of antibacterial benefit and colistin nephrotoxicity for different dosing regimens via simulations.
A prospective popPK study included 13 critically-ill patients treated with CMS and receiving SLED (6-8h) for renal support. The PK of formed colistin was studied on both a nonSLED and a SLED day. Colistin plasma concentrations were analysed using the popPK approach. Monte Carlo simulations (MCS) for dosing regimen evaluation were performed.
A linear one-compartment PK disposition model best described the data. The total body clearance of colistin (excluding SLED clearance) was 1.69L (21%) [population mean (between subject variability)] with 42% interoccasion variability. Colistin clearance during the SLED period was estimated to be 3.49L (42%). We evaluated the probability of target attainment defined as percentage of patients achieving relevant average colistin plasma concentration (Cavg) targets: >80% for Cavg ≥2 mg/L, >90% for Cavg ≥1.5 mg/L and <30% for Cavg ≥4 mg/L for the first 24h of therapy initiation on a SLED or nonSLED day as well as maintenance therapy.
Colistin clearance was substantially higher during SLED; therefore, SLED should be accounted for in CMS dosing regimens. This analysis provides comprehensive information regarding the achievement of clinically desirable average plasma colistin concentrations (including evaluation of loading doses) for two dosing regimens and six different SLED administration scenarios.
Key words:
Population pharmacokinetic modelling, colistin, sustained low-efficiency dialysis
Biography
Dominika is a PhD candidate at the Monash Institute of Pharmaceutical Sciences, Monash University. Her PhD research focuses on the development of novel mechanism-based mathematical models as well as population pharmacokinetic models. She’s passionate about investigating ways to treat resistant bacterial “superbugs” by optimising dosing regimens of currently available antibiotics in the fight against antimicrobial resistance
A/Prof Xiao Zhu
Associate Professor of Pharmacometrics
Fudan University
Model-informed precision dosing of anti-infective drugs in paediatrics
Biography
Session chair
Shaun Kumar
Associate Director
Parexel International
Austin Tan
National University of Singapore
