Pharmacokinetics of a novel, transdermal fentanyl solution in rhesus macaques (Macaca mulatta)

Gregory W. Salyards, Marie Josee Lemoy, Heather K Knych, Ashley E Hill, Kari L. Christe

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Rhesus macaques (Macaca mulatta) are the most commonly used NHP biomedical model and experience both research and clinical procedures requiring analgesia. Opioids are a mainstay of analgesic therapy. A novel, transdermal fentanyl solution (TFS) has been developed as a long-acting, single-administration topical opioid and was reported to provide at least 4 d of effective plasma concentrations in beagles (Canis familiaris). To evaluate the pharmacokinetic profile of TFS in healthy adult rhesus macaques, we used a 2-period, 2-treatment crossover study of a single topical administration of 1.3 (25) and 2.6 mg/kg (50 μL/kg) TFS. TFS was applied to the clipped dorsal skin of adult rhesus macaques (n = 6; 3 male, 3 female) under ketamine sedation (10 mg/kg IM). We hypothesized that TFS in rhesus macaques would provide at least 4 d of effective plasma concentrations (assumed to be ≥ 0.2 ng/mL, based on human studies). Plasma fentanyl concentrations were determined by liquid chromatography-tandem mass spectrometry before drug administration and at 0, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 240, 336, 408, and 504 h afterward. Noncompartmental pharmacokinetic analysis was performed. For each dose (1.3 and 2.6 mg/kg), respectively, the maximal plasma concentration was 1.95 ±0.40 and 4.19 ±0.69 ng/mL, occurring at 21.3 ±4.1 and 30.7 ±8.7 h; the AUC was 227.3 ±31.7 and 447.0 ±49.1 h/ng/mL, and the terminal elimination half-life was 93.7 ±7.1 and 98.8 ±5.4 h. No adverse effects were noted after drug administration at either dose. Macaques maintained plasma fentanyl concentrations of 0.2 ng/mL or greater for at least 7 d after 1.3 mg/kg and at least 10 d after 2.6 mg/kg topical administration of TFS. A single TFS dose may provide efficacious analgesia to rhesus macaques and reduce stress, discomfort, and risk to animals and personnel.

Original languageEnglish (US)
Pages (from-to)443-451
Number of pages9
JournalJournal of the American Association for Laboratory Animal Science
Volume56
Issue number4
StatePublished - Jul 1 2017

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fentanyl
Macaca mulatta
pharmacokinetics
narcotics
analgesia
dosage
drugs
sedation
ketamine
analgesics
Beagle
Macaca
skin (animal)
liquid chromatography
human resources
half life
adverse effects
therapeutics
dogs

ASJC Scopus subject areas

  • Animal Science and Zoology

Cite this

Pharmacokinetics of a novel, transdermal fentanyl solution in rhesus macaques (Macaca mulatta). / Salyards, Gregory W.; Lemoy, Marie Josee; Knych, Heather K; Hill, Ashley E; Christe, Kari L.

In: Journal of the American Association for Laboratory Animal Science, Vol. 56, No. 4, 01.07.2017, p. 443-451.

Research output: Contribution to journalArticle

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AU - Christe, Kari L.

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