title: Optimizing the dosing interval of buprenorphine in a multimodal postoperative analgesic strategy in the rat: minimizing side-effects without affecting weight gain and food intake.
abstract: Buprenorphine is commonly used as (part of) postoperative analgesic treatment with dosage dependent side-effects such as pica behaviour. No strict consensus exists about the optimal dosing interval of buprenorphine, as its duration of action has been described as being in the range of 6-12 h. In this study, dosing intervals of 8 h (thrice-a-day) and 12 h (twice-a-day) for buprenorphine in a multimodal analgesic strategy (concurrent administration of a non-steroidal anti-inflammatory drug) were compared on food intake, weight and side-effects (gnawing on plastic Petri dishes and growth rate, indicative of pica behaviour) in rats. The food intake and weight of both intervals were comparable, as the animals from the twice-a-day group did not lose more weight or consumed less food during the analgesic period. The rats from the thrice-a-day group suffered from more side-effects, as the growth rate was decreased and more plastic was gnawed on. It is recommended to carefully evaluate analgesic and side-effects when using buprenorphine. When side-effects are observed, the possibility of increasing the dosing interval of buprenorphine should be explored. In this study, increasing the dosing interval of buprenorphine in a multimodal analgesic regimen resulted in reduced unwanted side-effects, without increasing weight loss or decreasing food intake. Although this is suggestive of provision of comparable analgesia, future studies including more pain-related readout parameters to assess the effect of the dosing interval on analgesic efficacy are recommended.
authors.affiliation: Division of Anesthesiology & Neurophysiology, Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 2, PO Box 80.166, 3584 CM Utrecht, The Netherlands. m.schaap@uu.nl
authors.forename: Manon W H
authors.initials: MW
authors.lastname: Schaap
authors.forename: Joost J
authors.initials: JJ
authors.lastname: Uilenreef
authors.forename: Manuela D
authors.initials: MD
authors.lastname: Mitsogiannis
authors.forename: José G
authors.initials: JG
authors.lastname: van 't Klooster
authors.forename: Saskia S
authors.initials: SS
authors.lastname: Arndt
authors.forename: Ludo J
authors.initials: LJ
authors.lastname: Hellebrekers
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D002047:Buprenorphine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000662:veterinary; D004567:Electrodes, Implanted / Q000662:veterinary; D005247:Feeding Behavior; D007279:Injections, Subcutaneous / Q000662:veterinary; D008297:Male; D000077239:Meloxicam; D019635:Neurosurgical Procedures / Q000662:veterinary; D010149:Postoperative Pain / Q000188:drug therapy / Q000517:prevention & control / Q000662:veterinary*; D010842:Pica / Q000139:chemically induced*; D011182:Postoperative Care / Q000662:veterinary; D051381:Rats / Q000601:surgery; D017208:Rats, Wistar; D013843:Thiazines / Q000008:administration & dosage; D013844:Thiazoles / Q000008:administration & dosage; D013997:Time Factors; D015430:Weight Gain
chemical_list: D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D013843:Thiazines; D013844:Thiazoles; D002047:Buprenorphine; D000077239:Meloxicam