Pharmacokinetics, pharmacodynamics and pharmacogenetics associated with nonsteroidal anti-inflammatory drugs and opioids in pediatric cancer patients

ABSTRACT

Introduction: Advancing appropriate and adequate analgesic pharmacotherapy in pediatric patients with cancer is an area of clinical need. Few studies have been performed to evaluate the selection of an analgesic and appropriate dosing corresponding to analgesic effect among pediatric cancer patients. This review describes information related to pharmacokinetic, pharmacodynamic, and pharmacogenomic (when applicable) considerations for analgesics that are commonly used to manage pain experienced by pediatric patients with cancer.

Areas covered: Analgesics commonly used to treat pediatric patients with malignancy patterned after the World Health Organization’s ‘analgesic ladder’ for cancer pain management.

Expert opinion: Addressing pain management safely and effectively in pediatric patients with cancer will require advances in both drug development, to increase the armament of analgesics available for children, and our pharmacologic understanding of those analgesics in current use. However, performing the necessary types of studies to develop new analgesics, or gain knowledge of existing therapy, within a population that is relatively small, diverse, and who experience pain originating from a variety of sources, is a tremendous challenge.

KEYWORDS:

• Cancer
• non-steroidal anti-inflammatory drugs
• opioids
• pediatric
• pharmacodynamics
• pharmacogenetics
• pharmacogenomics
• pharmacokinetics

Article highlights

• Advancing appropriate and adequate analgesic pharmacotherapy in pediatric patients with cancer is an area of clinical need.

• Few studies have been performed to evaluate the selection of an analgesic and appropriate dosing corresponding to analgesic effect among pediatric cancer patients.

• Despite much effort on this front in the last 25-30 years, conditions such as small sample sizes, differing and complex pain etiologies, and limitations inherent in the drugs available for pediatric patients with cancer, pose substantial challenges to attain precision and personalized analgesic regimens based on fully elucidated PK/PD/PGx.

• The complex etiology of pain, including episodes of breakthrough pain, is not well understood and forms a vital component to matching appropriate analgesic therapy to achieve a desired pharmacodynamic endpoint in pediatric patients

• Efforts to provide evidence-based pain management standards for pediatric and adult patients with cancer is ongoing and aim to provide much needed guidance for the treatment of pediatric patients with cancer.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded