Pharmacokinetics of low-dose and high-dose buprenorphine in cats after rectal administration of different formulations

Abstract

Objectives A prospective experimental study was performed in nine young healthy cats to investigate a pharmacokinetic profile and the clinical relevance of rectally administered buprenorphine. Rectal pH value was measured in all nine cats. Methods Blood was collected 15, 30, 60, 90, 120, 240 and 480 mins and 24 h after the rectal administration of a suppository and a gel at doses between 0.02 mg/kg and 0.1 mg/kg buprenorphine to determine the plasma concentration of buprenorphine. Rectal pH was measured with pH paper. Results Upon pharmacokinetic non-compartment analysis of high-dose buprenorphine (0.1 mg/kg), average maximal plasma concentration was found to be 1.13 ng/ml, time to maximal plasma concentration was 45 mins and area under the plasma concentration–time curve was 94.19 ng*min/ml, representing low but potential bioavailability. Mean residual time was 152.2 mins and the half-life was 92.6 mins. A wide range of plasma concentrations within the cohort was measured and two of the cats had to be excluded from statistical analysis owing to incomplete uptake. Vital parameters of all cats were considered to be normal but three of the cats showed mydriasis up to 8 h after application. After the administration of a low-dose suppository or a rectal gel (0.02 mg/kg) within pilot studies, no buprenorphine was detected in cat plasma. Rectal pH in all cats was between 7.7 and 8. Conclusions and relevance The rectal application of buprenorphine at a dose of 0.1 mg/kg revealed a potential but weak uptake in cats. Regarding effective concentrations in previous pharmacokinetic investigations, rectal administration is currently not recommended for good provision of opioid analgesia in cats. Pharmacological investigations of formulation and galenics in order to improve the rectal bioavailability of buprenorphine remain to be clarified before further dose-finding and pharmacokinetic/pharmacodynamic studies are performed.

Comparison of Certain Intrarectal versus Intramuscular Pharmacodynamic Effects of Ketamine, Dexmedetomidine and Midazolam in Cats

“…As for intraoral administration, the physicochemical characteristics of the molecule could result in reduced absorption through the rectal mucosa [ 15 ]. An increase in doses could lead to clinical effects comparable to those of the IM route, as demonstrated by the transmucosal route in healthy cats in combination with buprenorphine [ 31 ] and encouraging effects of IR route in cats for analgesia [ 13 ].…”

“…In veterinary medicine, IR administration is extensively investigated for the control of epileptic seizures in dogs, but less so in cats [ 10 , 11 ]. Unfortunately, there is still insufficient knowledge in the veterinary literature on the bioavailability of opioids, dexmedetomidine, and ketamine after IR administration [ 12 , 13 ]. Compared to other routes, it could have some advantages: faster and more predictable sedation action than OS administration, less physical trauma, and it is less painful than the IM and IV routes [ 14 ].…”

The history and pharmacology of buprenorphine: New advances in cats

“…In another study, the systemic exposures of two suppository formulations were compared following rectal administration (Schroers et al, 2019). These were compounded from human-approved sublingual tablets and gel from the human-approved injectable solution (0.3 mg/ml) at 0.02 and 0.1 mg/kg doses, respectively.…”

A Comparison of the Intrarectal and Intramuscular Effects of a Dexmedetomidine, Ketamine and Midazolam Mixture on Tear Production in Cats: A Randomized Controlled Trial

“…Furthermore, correct management of the venous catheter to prevent different complications such as extravasal administration, inflammation and/or phlebitis is desirable [ 11 , 12 ]. In recent years, in dogs and cats, attention has been paid to the efficacy and safety of sedative and analgesic drugs that are administered by alternative routes such as oral (OS), trans-mucosal (TM), intranasal (IN) and intrarectal (IR) [ 5 , 13 , 14 , 15 , 16 , 17 ]. For the IR route, few studies on the efficacy and complications of anesthetic and analgesic drugs are published.…”