Increase of cytochrome P450IA2 activity by omeprazole: Evidence by the 13 C‐[ N ‐3‐methyl]‐caffeine breath test in poor and extensive metabolizers of S ‐mephenytoin

Omeprazole has been shown to induce cytochrome P450IA1 and P450IA2 activity in vitro. To reflect cytochrome P450IA2 (CYP1A2) activity in vivo, the 13 C‐[ N ‐3‐methyl]‐caffeine breath test was conducted in 18 volunteers: 12 extensive metabolizers, one intermediate metabolizer, and five poor metabolizers of S ‐mephenytoin. Breath tests were performed before treatment with an oral dose of 40 mg omeprazole, on the seventh day of treatment, and after a 7‐day washout period. The mean percentage exhalation of the 13 C test dose, as determined by 13 CO 2 in breath during 8 hours, was 23.0% ± 8.0% ( n = 18) before treatment. The largest increases in exhalation rate of 13 CO 2 were observed in the poor metabolizers and the intermediate metabolizers (range, 12.8% to 62.9%; median, 38.9%); median area under the plasma concentration—time curves (AUC) of omeprazole was four times higher than in the extensive metabolizers. The change after omeprazole treatment in extensive metabolizers ranged from −9.8% to +47.7% (median, 12.3%; n = 12) of pretreatment values. In both groups exhalation rates of 13 CO 2 returned to near pretreatment values within the 7‐day washout period (24.2% ± 7.8%; n = 17). Changes in the 13 C‐caffeine breath test correlated well with both the pretreatment value ( R = −0.67, p = 0.003; n = 18) and the plasma AUC of omeprazole ( R = 0.61, p = 0.007; n = 18). Therapeutic doses of omeprazole seem to induce CYP1A2 activity in poor metabolizers, whereas they exert minor inducing effects in extensive metabolizers of S ‐mephenytoin. Clinical Pharmacology and Therapeutics (1992) 52, 170–180; doi: 10.1038/clpt.1992.126