Patterns of Neonatal Co-Exposure to Gabapentin and Common Drugs of Abuse Observed in Umbilical Cord Tissue
Authors: Okoye Nkemakonam , McMillin Gwendolyn 
Published: October 2020

Abstract

Background
Gabapentin is a structural analogue of gamma-aminobutyric acid approved by the U.S. Food and Drug Administration (FDA) for the treatment of postherpetic neuralgia and partial-onset seizures. Gabapentin is thought to have low abuse potential and is currently not scheduled as a controlled substance by the Drug Enforcement Administration (DEA). However, recent reports indicate that gabapentin is increasingly being abused by people with opioid use disorder in an attempt to potentiate the euphoric effects from opioids and other CNS depressants. (1) In 2018, Gabapentin was the sixth most commonly prescribed medication in the United States with 67 million prescriptions dispensed. (2) The frequency of non-prescribed gabapentin misuse reported at a reference laboratory increased by 40% between 2017 and 2018. (3) It is now recognized that combination of Gabapentin with opioids and other CNS depressants increases risk of respiratory depression. (4) Of particular concern are reports showing prolonged and more severe neonatal abstinence syndrome in infants with prenatal co-exposure to gabapentin and opioids. (5)

Method
This retrospective study evaluated the positivity rates of 13,609 umbilical cord tissues submitted for newborn drug testing at ARUP Laboratories. The umbilical cord drug detection assay is designed to detect 49 specific drugs and drug metabolites from commonly abused drug classes including opioids, stimulants, sedative-hypnotics and hallucinogens. Reverse phase liquid chromatography coupled with triple quadrupole mass spectrometry was used for semi-quantitative measurement of the drug analytes and metabolites.

Results
A positive result for at least one of the measured drugs or drug metabolites was found in 3,891 (29%) out of the 13,609 analyzed umbilical cord tissues. Norbuprenorphine had the highest positivity rate (874, 6%) followed by Amphetamine (764, 6 %) and Morphine (683, 5%). Gabapentin had a positivity rate of 2% with 302 positive results. Of the 302 positive Gabapentin samples, 216 (72%) also had a positive result for at least one other drug or drug metabolite. Co-positivity with Gabapentin was highest for Norbuprenorphine (105, 35%) followed by Amphetamine (41, 14%). The median Gabapentin concentration in umbilical cord tissues that were co-positive for Norbuprenorphine and Amphetamine is 3,762 ng/g (range = 13 - 40,997 ng/g) and 1,045 ng/g (range = 15 - 40,997 ng/g) respectively.

Discussion
This retrospective data analysis show that there is high neonatal co-exposure rate to Gabapentin and Buprenorphine / Norbuprenorphine. Buprenorphine is a partial mu-opioid receptor agonist and co-medication with Gabapentin might be used as a strategy to enhance the feeling of euphoria from Buprenorphine in pregnant women undergoing opioid substitution therapy.

References
1. Drugs 77, 403–426 (2017)
2. Medicine Use and Spending in the U.S. A Review of 2018 and Outlook to 2023
3. https://www.questdrugmonitoring.com/healthtrends (Accessed January 2020)
4. https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-breathing-problems-seizure-and-nerve-pain-medicines-gabapentin-neurontin (Accessed January 2020)
5. The Journal of Pediatrics 181, 286–288 (2017)