Table 2

Effect of protease inhibitors (at concentration equal to Ki) on the N-dealkylation of methadone (M) and buprenorphine (B) in 13 human liver microsomal preparations

Concentration (μM)Microsomal SamplesMeanSD
Protease Inhibitor2-aSubstrate2-aBrMBr21Br33Br34Br35Br36Br37Br39Br43Br48Br66Br67Br062
[R] = 0.05[M] = 50066.973.876.6ND33.051.030.426.316.727.886.734.550.747.923.2
[R] = 0.05[B] = 10035.638.490.2ND102.030.588.961.188.4122.
[I] = 3[M] = 50028.952.635.7ND64.432.844.643.951.060.249.739.655.246.511.0
[I] = 1[B] = 10041.455.348.0ND74.147.848.058.677.848.660.539.456.754.711.9
[S] = 15[M] = 50051.448.858.9ND79.147.940.250.666.063.654.750.661.256.110.3
[S] = 7[B] = 10074.557.4ND58.287.649.053.656.775.285.874.334.886.366.116.9
  • Results are expressed as percent of control activity, without inhibitor but with the same amount of solvent that was needed for inhibitor addition.

  • 2-a R, ritonavir; S, saquinavir; I, indinavir; M, methadone; B, buprenorphine; ND, not determined. Concentrations are expressed in μmol/liter.