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Perpetrators of pharmacokinetic drug–drug interactions: criteria-based assessment of medicines registered since 2011

A 2019/2020 Summer Studentship research project

Drug interactions are a cause of harm and of treatment failure. Polypharmacy is increasing and this increases the frequency of drug interactions. Accurately identifying medicines that cause drug interactions can help improve prescribing and reduce drug interactions. This project will build on previous work to identify which medicines used in New Zealand are most likely to cause drug interactions. The project will look at all medicines registered in New Zealand or Australia since 2011. The results will be used to update clinical resources in current use for drug interactions.

Student: Rutvi Soni
Supervisors: Associate Professor Matt Doogue, Dr Paul Chin (UOC), Dr Tom Polasek (Flinders University)
Sponsor: University of Otago, Christchurch

Introduction

Pharmacokinetic drug–drug interactions (PK-DDIs) contribute to failure of drug therapy, either from toxicity leading to patient harm or sub-therapeutic concentrations resulting in loss of efficacy. PK-DDIs are difficult for clinicians to identify and standard reference sources are inconsistent. Commercially available DDI checkers usually over-alert with >90 per cent of DDI alerts being overridden in standard systems. We have previously found, using internationally agreed criteria, that many perpetrators of PK-DDIs are misclassified. 1Accurate classification of perpetrators of PK-DDIs reduces alerts and reduces prescribing errors.

Aim

To determine the major perpetrators of pharmacokinetic drug–drug interactions (PK-DDIs) using clinically relevant criteria for medicines registered in New Zealand since 2011.

Method

Candidate inhibitors and inducers of drug metabolising enzymes will be identified from existing medicines information resources. For each potential “perpetrator” a standardised literature search will be undertaken to identify clinical pharmacokinetic interaction studies. Inhibitors and inducers will be classified based on the change in area under the concentration time curve (AUC) of established CYP-450 probe drugs. The results will be incorporated into existing clinical resources including MedChart™, the prescribing software currently used at CDHB hospitals.

Student researcher’s component of the study

Using lists of “possible” perpetrators, the student will undertake standardized literature searches to quantify the inhibition or induction of drug metabolism in human pharmacokinetics. Studies will be reviewed together with supervisors. These results will be used to define the potential for pharmacokinetic drug interactions. The student will be supported to publish the results. The results of this study will be used to update clinical resources (www.pkis.org).

  1. Polasek TM, Lin FP, Miners JO, Doogue MP. Perpetrators of pharmacokinetic drug-drug interactions arising from altered cytochrome P450 activity: a criteria-based assessment. Br J Clin Pharmacol. 2011 May;71(5):727-36. doi: 10.1111/j.1365-2125.2011.03903.x.

Student Prerequisites

A medical or pharmacy student with an interest in medicines and learning literature review and simple data analysis.

How to apply

Email matt.doogue@otago.ac.nz