Clinical and pharmacological evaluation of buprenorphine and naloxone combinations: why the 4:1 ratio for treatment?

Although only a partial μ-opiate agonist, buprenorphine can be abused and diverted from medical therapy to the illicit drug market. A combination of buprenorphine and naloxone for sublingual administration may discourage diversion and abuse by precipitating opiate withdrawal when taken parenterally. Because opiate-abusing populations are not homogeneous and have varying levels of opiate dependence, the efficacy of buprenorphine and naloxone in precipitating opiate withdrawal or in attenuating the pleasurable effects of buprenorphine may vary. This chapter describes the effects of sublingual and parenteral buprenorphine and naloxone combinations in several populations of opiate-dependent people. We conclude that buprenorphine and naloxone combinations should not diminish the efficacy of sublingual buprenorphine, but should have lower abuse liability than buprenorphine alone.