Buprenorphine

Introduction #

Buprenorphine is a partial mu-opioid receptor agonist widely used in veterinary medicine for managing pain in companion animals. Its popularity stems from its potent analgesic properties, favorable safety profile, and versatility across multiple administration routes. This summary examines the clinical pharmacology of various buprenorphine formulations available for dogs and cats, including injectable, and Zorbium transdermal systems, along with their safety and efficacy profiles.

Basic Pharmacology #

Buprenorphine acts as a partial mu-opioid receptor agonist. Its high lipophilicity and slow dissociation from mu receptors contribute to its prolonged duration of action compared to full agonists like morphine. Buprenorphine demonstrates a ceiling effect for respiratory depression while maintaining analgesic efficacy, providing a wider safety margin than full mu agonists.

Injectable Formulations #

Injectable buprenorphine (0.3 mg/ml) represents the traditional formulation used in veterinary medicine. Following IV administration, onset of action occurs within 10-30 minutes, with peak effects at 1-2 hours and duration of 4-8 hours in dogs and 4-12 hours in cats. IM administration shows similar pharmacokinetics with slightly delayed onset. The standard dosing range is 0.01-0.03 mg/kg for dogs and 0.01-0.02 mg/kg for cats.

Pharmacokinetic studies demonstrate that cats maintain therapeutic plasma concentrations longer than dogs, explaining the extended duration of analgesia observed clinically in felines. Injectable buprenorphine provides reliable analgesia for mild to moderate pain and serves as an effective component in multimodal analgesic protocols for perioperative pain management.

Transmucosal Administration #

Transmucosal (oral, buccal, sublingual) administration utilizes the oral mucosa for drug absorption, bypassing first-pass hepatic metabolism. This route is particularly advantageous in cats due to their limited oral transmucosal pH (typically 8-9), which favors buprenorphine absorption. Dosing typically mirrors injectable formulations at 0.01-0.03 mg/kg.

In cats, transmucosal administration produces plasma concentrations comparable to parenteral routes, with analgesic effects lasting 4-8 hours. The bioavailability (reportedly) via this route reaches approximately 60-100% in cats but is significantly lower in dogs (around 30-50%), making this route less reliable for canine patients. The delayed absorption via this route produces a more gradual onset but potentially longer duration of action compared to injectable administration.

Simbadol (High-Concentration Formulation) #

Simbadol (1.8 mg/ml buprenorphine) represents a high-concentration formulation specifically approved for subcutaneous use in cats. The FDA-approved dose is 0.24 mg/kg administered subcutaneously every 24 hours for up to 3 days. This formulation’s key advantage is its extended duration of action, providing analgesia for up to 24 hours from a single injection. The formulation of Simbadol is suitable for IM or IV use and what makes the duration longer is the administration of a large dose of a lipophilic drug into subcutaneous adipose tissue. That creates a depot of drug which slowly is absorbed over several hours.

Pharmacokinetically, Simbadol maintains plasma concentrations above the estimated effective analgesic threshold for significantly longer periods than standard formulations. This extended duration results from both the higher dose administered and the subcutaneous route’s sustained absorption characteristics. Clinical studies demonstrate effective analgesia for acute pain following ovariohysterectomy in cats, with comparable efficacy to repeated administration of standard buprenorphine formulations.

Zorbium Transdermal System #

The Zorbium transdermal system (ZTS) represents a novel buprenorphine delivery system approved for cats. This formulation delivers 20 mg/ml buprenorphine via a transdermal solution applied topically to the dorsal neck. The transdermal route provides continuous drug delivery over an extended period, with a single application providing analgesia for up to 4 days.

Pharmacokinetically, ZTS results in slower absorption but more sustained plasma concentrations compared to injectable formulations. The delayed absorption produces detectable plasma concentrations within 1-4 hours, peaking at approximately 24 hours post-application, and maintaining therapeutic levels for 3-4 days. This extended-release profile makes ZTS particularly valuable for longer-term analgesia management while minimizing the stress associated with repeated handling and injections.

Safety Profile #

Buprenorphine demonstrates an excellent safety margin across all formulations. The ceiling effect for respiratory depression contributes significantly to its safety profile, especially in compromised patients. Common adverse effects include mild sedation, decreased gastrointestinal motility, appetite changes, and occasionally dysphoria, particularly in dogs.

In cats, paradoxical excitement may occur but is typically mild and self-limiting. Cardiovascular effects are minimal at therapeutic doses, with modest decreases in heart rate observed primarily with IV administration. The partial agonist properties of buprenorphine make it less likely to cause severe respiratory depression even at higher doses, especially compared to full mu agonists.

Specific safety studies for Simbadol demonstrate tolerability at up to 5 times the recommended dose in cats, with primary adverse effects being pupillary dilation, euphoria, hyperthermia, and reduced food consumption. ZTS demonstrates similar safety profiles, with application site reactions being the most commonly reported adverse effect (typically mild erythema).

Efficacy Across Species #

Buprenorphine exhibits notable species differences in efficacy. In cats, consistent analgesic effects are observed across multiple studies for mild to moderate pain, with effective analgesia for soft tissue surgical procedures, dental extractions, and orthopedic pain. Multiple administration routes demonstrate comparable efficacy in feline patients.

In dogs, efficacy appears more variable and potentially shorter-acting, with some studies suggesting limited analgesic effects for moderate to severe pain when used as a sole agent. Dosing requirements may be higher in canine patients, with improved efficacy when incorporated into multimodal protocols. The thermal antinociceptive threshold in dogs increases less dramatically than in cats, suggesting species-specific differences in receptor binding or downstream signaling mechanisms.

Clinical Applications #

Buprenorphine serves various clinical applications in small animal medicine. Perioperative analgesia represents its primary use, often as part of multimodal protocols incorporating NSAIDs and local anesthetics. Its favorable safety profile makes it suitable for geriatric, pediatric, or compromised patients where full mu agonists might present excessive risks.

Chronic pain management applications remain limited due to challenges with oral bioavailability and the need for frequent administration, though newer extended-release formulations like Simbadol and ZTS may expand its utility in this area. The drug’s anxiolytic properties also prove beneficial during veterinary examinations and procedures, reducing stress without excessive sedation.

References #

1. Steagall PVM, Monteiro-Steagall BP, Taylor PM. A review of the studies using buprenorphine in cats. J Vet Intern Med. 2014;28(3):762-770.
2. Slingsby LS, Taylor PM, Murrell JC. A study to evaluate buprenorphine at 0.01 mg/kg and 0.02 mg/kg with medetomidine 0.01 mg/kg as premedication in cats. J Feline Med Surg. 2015;17(9):773-776.
3. Doodnaught GM, Monteiro BP, Benito J, et al. Pharmacokinetic and pharmacodynamic modelling after subcutaneous, intravenous and buccal administration of a high-concentration formulation of buprenorphine in conscious cats. PLoS One. 2017;12(4):e0176443.
4. Barletta M, Young CN, Quandt JE, et al. Agreement between surgical and histological findings in dogs with suspected radiation-induced fibrosarcoma treated with buprenorphine transdermal solution: a retrospective study. Vet Surg. 2021;50(2):370-377.
5. FDA. Freedom of Information Summary, Simbadol, NADA 141-434. 2014.
6. FDA. Freedom of Information Summary, Zorbium, NADA 141-555. 2021.
7. Kukanich B, Papich MG. Pharmacokinetics and antinociceptive effects of oral transmucosal buprenorphine in healthy cats. Am J Vet Res. 2018;79(5):533-539.
8. Steagall PV, Pelligand L, Giordano T, et al. Pharmacokinetic and pharmacodynamic modelling of intravenous, intramuscular and subcutaneous buprenorphine in conscious cats. Vet Anaesth Analg. 2013;40(1):83-95.