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 (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.
Bendriss
E K
EK
Department of Clinical Pharmacology, Besançon University Hospital, France.
Bechtel
Y
Y
Bendriss
A
A
Humbert
P H
PH
Paintaud
G
G
Magnette
J
J
Agache
P
P
Bechtel
P R
PR
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*
D000697:Central Nervous System Stimulants; D002110:Caffeine; D000078223:5-Methoxypsoralen; D008730:Methoxsalen