Long-Acting Opioid Analgesics for Acute Pain: Pharmacokinetic Evidence Reviewed

Abstract

Long-acting injectable (LAI) opioid formulations mitigate the harm profiles and management challenges associated with providing effective analgesia for animals. A single dose of a long-acting opioid analgesic can provide up to 72 h of clinically relevant pain management. Yet, few of these new drugs have been translated to products for veterinary clinics. Regulatory pathways allow accelerated drug approvals for generic and biosimilar drugs. These pathways depend on rigorous evidence for drug safety and pharmacokinetic evidence demonstrating bioequivalence between the new and the legacy drug. This report reviews the animal PK data associated with lipid and polymer-bound buprenorphine LAI formulations. Buprenorphine is a widely used veterinary opioid analgesic. Because of its safety profile and regulatory status, buprenorphine is more accessible than morphine, methadone, and fentanyl. This review of PK studies coupled with the well-established safety profile of buprenorphine suggests that the accelerated approval pathways may be available for this new family of LAI veterinary pharmaceuticals.

Fentanyl activates opposing opioid and non-opioid receptor systems that control breathing

“…The high-potency μ-opioid receptor agonist, fentanyl, is an important clinical analgesic that has adverse side effects, including ventilatory depression and the development of hyperalgesia (enhanced pain perception) upon repeated administration ( Scholz et al, 1996 ; Suzuki and El-Haddad, 2017 ; Armenian et al, 2018 ; Tyler and Guarnieri, 2023 ). In addition, although the systemic injection of fentanyl causes profound analgesia in rats, it also exerts adverse effects on ventilatory parameters, the alveolar–arterial (A-a) gradient (index of alveolar gas exchange), and arterial blood–gas chemistry ( Henderson et al, 2014 ; Baby et al, 2021 ; Jenkins et al, 2021 ; Getsy et al, 2022a ; Getsy et al, 2022b ; Seckler et al, 2022 ; Marchette et al, 2023 ).…”