title: Inhibition of caffeine metabolism by 5-methoxypsoralen in patients with psoriasis.
abstract: 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 (CLp.o.) decreased from 9.5 +/- 3.8 (mean +/- s.d.) to 3.2 +/- 0.51 h-1 (P < 0.01). The area under the plasma concentration-time curve (AUC) increased from 24 +/- 9 to 73 +/- 29 mg 1(-1) h (P < 0.001). This decrease in CLp.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.
authors: Department of Clinical Pharmacology, Besançon University Hospital, France.
authors: E K
authors: EK
authors: Bendriss
authors: Y
authors: Y
authors: Bechtel
authors: A
authors: A
authors: Bendriss
authors: P H
authors: PH
authors: Humbert
authors: G
authors: G
authors: Paintaud
authors: J
authors: J
authors: Magnette
authors: P
authors: P
authors: Agache
authors: P R
authors: PR
authors: Bechtel
mesh_terms: D000078223:5-Methoxypsoralen; D000328:Adult; D000368:Aged; D002110:Caffeine / Q000097:blood / Q000378:metabolism* / Q000652:urine; D000697:Central Nervous System Stimulants / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D008730:Methoxsalen / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology / Q000652:urine; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*
chemical_list: D000697:Central Nervous System Stimulants; D002110:Caffeine; D000078223:5-Methoxypsoralen; D008730:Methoxsalen