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

• Published in: British journal of clinical pharmacology Vol. 41; no. 5; pp. 421 - 424
• Main Authors: BENDRISS, E. K., BECHTEL, Y., BENDRISS, A., HUMBERT, Ph, PAINTAUD, G., MAGNETTE, J., AGACHE, P., BECHTEL, P. R.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford Blackwell Science Ltd 01.05.1996; Blackwell Science
• Subjects: 5-Methoxypsoralen; 5‐methoxypsoralen caffeine metabolism inhibition CYP1A2; Adult; Aged; Biological and medical sciences; Caffeine - blood; Caffeine - metabolism; Caffeine - urine; Central Nervous System Stimulants - blood; Central Nervous System Stimulants - metabolism; Central Nervous System Stimulants - urine; Female; Humans; Male; Medical sciences; Methoxsalen - analogs & derivatives; Methoxsalen - blood; Methoxsalen - pharmacology; Methoxsalen - urine; Middle Aged; Miscellaneous; Original; Pharmacology. Drug treatments; Psoriasis - drug therapy; Consumption; Human; Skin disease; Psoriasis; Toxicity; Cytochrome P450; Interaction; Oral administration; Coffee; Metabolism; PUVA therapy; Food drug interaction; Psoralen derivatives; Caffeine
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1046/j.1365-2125.1996.33311.x

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±0.5 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 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.