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Inhibition of caffeine metabolism by 5‐methoxypsoralen in patients with psoriasis

1996; Wiley; Volume: 41; Issue: 5 Linguagem: Inglês

10.1046/j.1365-2125.1996.33311.x

1365-2125

El-khalil Bendriss, Y Bechtel, Abdenabi Bendriss, Ph. Humbert, Gilles Paintaud, J. Magnette, P Agache, P Bechtel,

Genomics, phytochemicals, and oxidative stress

Eight patients with psoriasis were given 200 mg caffeine orally with or without 1.2 mg kg −1 of 5‐methoxypsoralen. Blood and urine samples were collected over a 2‐day period. During 5‐methoxypsoralen coadministration, the apparent volume of distribution of caffeine remained unchanged, but oral clearance (CL p.o. ) decreased from 9.5±3.8 (mean±s.d.) to 3.2±0.5 l h −1 ( P <0.01). The area under the plasma concentration‐time curve (AUC) increased from 24±9 to 73±29 mg l −1 h ( P <0.001). This decrease in CL p.o. with increased AUC was consistent with a CYP1A2‐dependent inhibition of caffeine N ‐demethylation which was further supported by significant decreases in the (AFMU+1U+1X)/17U and (AFMU+1U+1X)/17X urinary metabolic ratios.