Table 2

Chemical inhibition of PZAa metabolismb

InhibitorsCYPcInhibitor (μm)Metabolite formation (% of control)
9-Desmethyl-PZAN-Demethyl-PZAPZA N-oxide
α-Naphthoflavone1A, 3A207418098
2005410851
Caffeine1A20868982
2009110182
Coumarind2A2009612989
Quinidine2D, 3A20849094
2009970105
Chlorzoxazoned2E, 1A2001028798
Tolbutamided2C200929197
Sulfaphenazoled2C200928899
Erythromycin3A20947998
2009234100
Quercitin3A, 1A20817885
200745978
MethimazoleFMOc20927181
200943533
  • a PZA, pyrazoloacridine; CYP, cytochrome P450; FMO, flavin monooxygenase.

  • b Values in the table represent metabolite formation in the presence of inhibitors as a percentage of metabolite formation in the absence of inhibitors after incubation of PZA with human liver microsomes.

  • c CYP isoforms inhibited by the chemicals listed in column 2. Methimazole is an inhibitor of FMO, but not CYP.

  • d If <15% inhibition at the high concentration, data for low concentration are not shown.