# Pharmacogenetics of Oxycodone, Personalized Care and Persistent Surgical Pain

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $445,859

## Abstract

Project Summary: In the US, >6 million children and >35 million adults undergo painful surgery each year.
While opioids are the preferred analgesics to reduce surgical pain, several deaths and serious adverse effects
such as respiratory depression occur with opioids especially in children. Further, up to 50% of these surgical
patients experience inadequate pain relief and/or serious adverse effects from perioperative opioids because
of their narrow therapeutic indices and unpredictable inter-individual variations among genetically dissimilar
patients. It took >20 years to recognize the life-threatening complications and deaths associated with codeine
from CYP2D6 genetic variations in children undergoing tonsillectomy and breastfed infants. As an alternative
to codeine, oxycodone is used more frequently in children undergoing tonsillectomy; and it had been shown
NOT to be a safe alternative to codeine for infants and nursing mothers. Currently, there is no evidence to
show that oxycodone is safer than codeine in children undergoing surgery. In addition, two potentially
preventable long-term complications are associated with major surgery and opioids: chronic persistent surgical
pain (CPSP) and opioid dependence/addiction (OD). All these preventable public health crises confer
unsustainable socioeconomic burden with loss of productive life. These adverse outcomes are currently
difficult to avoid due to a critical knowledge gap on inter-patient variations in pain perception and opioid
responses. Our long-term goals are to improve safety and efficacy of opioids in the immediate perioperative
perioid, and to mimimize the societal burden of disabling long-term problems, CPSP and OD by preoperative
risk predictions and personalized dosing and pain management with the right dose of the right analgesic for
each child. The overall objective is to determine the impact of genetic, psychological, sensory and
environmental risk factors associated with oxycodone's pharmacokinetics, surgical pain relief and adverse
outcomes, CPSP and OD in children. Our central hypothesis is that specific psychological and sensory factors
along with polymorphisms of genes involved in pain and opioid pathways significantly impact oxycodone's
clinical dosing, analgesia, immediate perioperative adverse effects including Respiratory Depression (RD) and
Post-Operative Nausea and Vomiting (PONV), and long-term adverse outcomes (CPSP and OD) in children.
The specific aims are 1) Determine genetic factors compromising safety and efficacy of oxycodone in children,
2) Determine the impact of CYP2D6 variants on oxycodone's clinical dosing, and 3) Identify genetic, immediate
perioperative and psychological factors predisposing children to long-term adverse outcomes: CPSP and OD.
This application is significant because it is expected to improve clinician's ability to preoperatively identify risks
of serious post-surgical problems in children and personalize perioperative care with tailored p...

## Key facts

- **NIH application ID:** 10006082
- **Project number:** 5R01HD089458-05
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Senthilkumar Sadhasivam
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $445,859
- **Award type:** 5
- **Project period:** 2016-09-22 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10006082

## Citation

> US National Institutes of Health, RePORTER application 10006082, Pharmacogenetics of Oxycodone, Personalized Care and Persistent Surgical Pain (5R01HD089458-05). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10006082. Licensed CC0.

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