Respiratory effects of buprenorphine/naloxone alone and in combination with diazepam in naive and tolerant rats.
Respiratory depression has been attributed to buprenorphine (BUP) misuse or combination with benzodiazepines. BUP/naloxone (NLX) has been marketed as maintenance treatment, aiming at preventing opiate addicts from self-injecting crushed pills. However, to date, BUP/NLX benefits in comparison to BUP alone remain debated. We investigated the plethysmography effects of BUP/NLX in comparison to BUP/solvent administered by intravenous route in naive and BUP-tolerant Sprague-Dawley rats, and in combination with diazepam (DZP) or its solvent. In naive rats, BUP/NLX in comparison to BUP significantly increased respiratory frequency (f, P<0.05) without altering minute volume (VE). In combination to DZP, BUP/NLX significantly increased expiratory time (P<0.01) and decreased f (P<0.01), tidal volume (VT, P<0.001), and VE (P<0.001) while BUP only decreased VT (P<0.5). In BUP-tolerant rats, no significant differences in respiratory effects were observed between BUP/NLX and BUP. In contrast, in combination to DZP, BUP/NLX did not significantly alter the plethysmography parameters, while BUP increased inspiratory time (P<0.001) and decreased f (P<0.01) and VE (P<0.001). In conclusion, differences in respiratory effects between BUP/NLX and BUP are only significant in combination with DZP, with increased depression in naive rats but reduced depression in BUP-tolerant rats. However, BUP/NLX benefits in humans remain to be determined.
Inserm, U1144, Paris F-75006, France; Université Paris Descartes, UMR-S 1144, Paris F-75006, France; Université Paris Diderot, UMR-S 1144, Paris F-75013, France.
Camille
C
Cohier
Inserm, U1144, Paris F-75006, France; Université Paris Descartes, UMR-S 1144, Paris F-75006, France; Université Paris Diderot, UMR-S 1144, Paris F-75013, France.
Lucie
L
Chevillard
Inserm, U1144, Paris F-75006, France; Université Paris Descartes, UMR-S 1144, Paris F-75006, France; Université Paris Diderot, UMR-S 1144, Paris F-75013, France.
Patricia
P
Risède
Inserm, U1144, Paris F-75006, France; Université Paris Descartes, UMR-S 1144, Paris F-75006, France; Université Paris Diderot, UMR-S 1144, Paris F-75013, France; IRCGN, département Toxicologie, Rosny sous-Bois, France.
Olivier
O
Roussel
Inserm, U1144, Paris F-75006, France; Université Paris Descartes, UMR-S 1144, Paris F-75006, France; Université Paris Diderot, UMR-S 1144, Paris F-75013, France; Assistance Publique - Hôpitaux de Paris, Hôpital Lariboisière, Réanimation Médicale et Toxicologique, 2 rue Ambroise Paré, 75010 Paris, France. Electronic address: bruno-megarbane@wanadoo.fr.
Bruno
B
Mégarbane
D000701:Analgesics, Opioid / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D002047:Buprenorphine / Q000633:toxicity*; D003975:Diazepam / Q000633:toxicity*; D004347:Drug Interactions; D004361:Drug Tolerance; D006993:Hypnotics and Sedatives / Q000633:toxicity*; D008297:Male; D009270:Naloxone / Q000633:toxicity*; D009292:Narcotic Antagonists / Q000633:toxicity*; D010993:Plethysmography, Whole Body; D051381:Rats; D017207:Rats, Sprague-Dawley; D012131:Respiratory Insufficiency / Q000139:chemically induced*
D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives; D009292:Narcotic Antagonists; D009270:Naloxone; D002047:Buprenorphine; D003975:Diazepam
Buprenorphine; Diazepam; Naloxone; Respiratory depression; Whole-body plethysmography