Lack of effect of single high doses of buprenorphine on arterial blood gases in the rat

High dose buprenorphine, a potent semisynthetic agonist-antagonist for opia te receptors, is now used in substitution treatment of human heroin addicti on. Deaths have been reported in addicts misusing buprenorphine. We determi ned the median lethal dose (LD50) and studied the effects of high doses of intravenous buprenorphine on arterial blood gases in rats. Male Sprague-Daw ley rats were administered buprenorphine intravenously to determine the LD5 0 using the up-and-down method. Subsequently, catheterized groups of 10 res trained rats received no drug, saline, acid-alcohol aqueous solvent (requir ed to dissolve buprenorphine at a high concentration), or 3, 30, or 90 mg/k g of buprenorphine intravenously. Serial arterial blood gases were obtained over 3 h. The LD50 determined in triplicate was 146.5 mg/kg (median of 3 s eries, range: 142.6-176.5). The mean dose received by surviving animals was 96.9 +/- 46.7 mg/kg. There was a significant effect of the acid-alcohol aq ueous solvent on arterial blood gases. Excluding the solvent effect, 3, 30, and 90-mg/kg buprenorphine doses had no significant effects on arterial bl ood gases. The toxicity of intravenous buprenorphine in adult rats, assesse d by the LD50, is low. These data are consistent with a wide margin of safe ty of buprenorphine. The mechanism of death after the intravenous administr ation of a lethal dose of buprenorphine remains to be determined.