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

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.