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. 2020 Sep 1:214:108147.
doi: 10.1016/j.drugalcdep.2020.108147. Epub 2020 Jul 2.

Protracted renal clearance of fentanyl in persons with opioid use disorder

Andrew S Huhn  1 , J Gregory Hobelmann  2 , George A Oyler  3 , Eric C Strain  4
Affiliations

Protracted renal clearance of fentanyl in persons with opioid use disorder

Andrew S Huhn et al. Drug Alcohol Depend. .

Abstract

Introduction: The illicit opioid supply in the U.S. is increasingly adulterated with fentanyl. As such, persons with opioid use disorder (OUD) may be regularly exposed to fentanyl, however, the pharmacokinetics of repeated fentanyl exposure are not well understood. The current study aimed to quantify renal clearance of fentanyl in OUD patients presenting to residential treatment.

Methods: Participants (N = 12) who presented to a 28-day residential treatment program were enrolled if they tested positive for fentanyl at intake. Urine samples were collected every 2-3 days and were quantitatively tested for fentanyl, norfentanyl, and creatinine via liquid chromatography mass spectrometry (LC-MS). Fentanyl clearance was defined as the time since last illicit opioid use and the median time between last positive and first negative fentanyl urine screen.

Results: Participants had a mean and standard deviation (SD) age of 28.9 (11.0), were 67 % male, and 83 % white. The mean (SD) time for fentanyl and norfentanyl clearance was 7.3 (4.9) and 13.3 (6.9) days, respectively. One participant continued to test positive for fentanyl for 19 days and norfentanyl for 26 days following their last use, and left treatment without testing negative for norfentanyl.

Conclusion: Fentanyl clearance in persons with OUD is considerably longer than the typical 2-4 day clearance of other short-acting opioids. The findings of this study might explain recent reports of difficulty in buprenorphine inductions for persons who use fentanyl, and point to a need to better understand the pharmacokinetics of fentanyl in the context of opioid withdrawal in persons who regularly use fentanyl.

Keywords: Fentanyl; Heroin; Opioid; Opioid use disorder; Pharmacokinetic; Treatment.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing interest. ASH receives research funding from Ashley Addiction Treatment through his university. ECS has served on advisory boards, received grant funding from, and/or consulted for Alkermes, Analgesic Solutions, Caron, Indivior Pharmaceuticals, Innocoll Pharmaceuticals, The Oak Group/VitalHub, UpToDate, Otsuka Pharmaceutical Development and Commercialization, and Pinney Associates. He has received honoraria from the World Health Organization, and is currently collaborating with Innovative Health Solutions. All other authors report no financial disclosures.

Figures

Figure 1.
Figure 1.
Mean time course for fentanyl and norfentanyl positive urine drug screens since day of last opioid use. Data is creatinine-adjusted and presented as nanogram of fentanyl/norfentanyl per milligram of creatinine. Data for participants who left against medical advice were censored following their last fentanyl positive test. Days with no urine screens were imputed for each individual based on a decay function for initial clearance and linear function for protracted clearance, consistent with trends observed in the data. The length of fentanyl and norfentanyl lines represents the longest time observed for positive urine screens since day of last use, which was 19 and 26 days, respectively. Error bars represent 95% confidence intervals.
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