title: Pharmacokinetics of 2 Formulations of Transdermal Fentanyl in Cynomolgus Macaques (Macaca fascicularis).
abstract: Fentanyl is a μ-opioid agonist that often is used as the analgesic component for balanced anesthesia in both human and veterinary patients. Minimal information has been published regarding appropriate dosing, and the pharmacokinetics of fentanyl are unknown in NHP. The pharmacokinetic properties of 2 transdermal fentanyl delivery methods, a solution (2.6 and 1.95 mg/kg) and a patch (25 μg/h), were determined when applied topically to the dorsal scapular area of cynomolgus macaques (Macaca fascicularis). Serum fentanyl concentrations were analyzed by using liquid chromatography-mass spectrometry. Compared with the patch, the transdermal fentanyl solution generated higher drug concentrations over longer time. Adverse reactions occurred in the macaques that received the transdermal fentanyl solution at 2.6 mg/kg. Both preparations showed significant interanimal variability in the maximal serum drug levels, time to achieve maximal fentanyl levels, elimination half-life, and AUC values. Both the maximal concentration and the time at which this concentration occurred were increased in macaques compared with most other species after application of the transdermal fentanyl patch and compared with dogs after application of the transdermal fentanyl solution. The pharmacokinetic properties of transdermal fentanyl in macaques are markedly different from those in other veterinary species and preclude its use as a long-acting analgesic drug in NHP.
authors.affiliation: Veterinary Medicine Division, The United States Army Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA. amy.m.carlson6.mil@mail.mil.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Carlson
authors.affiliation: Veterinary Medicine Division, The United States Army Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Kelly
authors.affiliation: Statistics, The United States Army Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Fetterer
authors.affiliation: Veterinary Medicine Division, The United States Army Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Rico
authors.affiliation: Veterinary Medicine Division, The United States Army Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Bailey
mesh_terms: D000279:Administration, Cutaneous; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D006207:Half-Life; D008252:Macaca fascicularis; D008297:Male; D013058:Mass Spectrometry; D010865:Pilot Projects; D011897:Random Allocation
chemical_list: D000701:Analgesics, Opioid; D005283:Fentanyl