Ceiling effect for respiratory depression by nalbuphine

Abstract

The respiratory depression [RD] capacities of i.v. nalbuphine [NB], a potent analgesic of the narcotic antagonist type, and of morphine [MP] were compared in 23 healthy human subjects using displacement of CO2 response by a steady-state method as the index of RD. At equianalgesic doses of 10 mg/70 kg, RD by NB was equal to that by MP. When increments of 10 mg/70 kg were given hourly the dose-effect curve for RD by NB was flatter than that of NP, and maximum RD occurred after 30 mg/70 kg. In a separate study of 10 subjects NB was administered in 10 mg/70 kg increments to a total dose of 60 mg/70 kg: doses in excess of 30 mg/70 kg failed to increase RD beyond that induced by MP 20 mg/70 kg. A ceiling effect for RD previously known to exist only for nalorphine was thereby demonstrated to apply to NB. The RD of NB was readily antagonized by naloxone 0.4 mg, nalorphine 10 mg and levallorphan 1.0 mg. Subjective effects of NB were milder than those of MP, and dysphoria suggestive of the psychotomimetic effects of narcotic antagonists was reported only 4 .times. in 24 subject exposures. The ceiling effect for RD by NB provides a unique safety factor among potent analgesics.