Liver cytochrome P450 CYP1A2 is markedly inhibited by systemic but not by bath PUVA in dermatological patients.
BACKGROUND
Methoxsalen (8-MOP) may cause important pharmacokinetic drug interactions as it has been shown to inhibit and/or induce several drug-metabolizing enzymes in vitro, in animal models and in humans.


OBJECTIVE
In order to assess the clinical importance of acute and chronic 8-MOP effects on the liver cytochrome P-450 enzyme CYP1A2 in vivo, we measured caffeine clearance in dermatological patients before the onset of systemic or bath psoralen + ultraviolet A radiation (PUVA) (8-MOP + UVA) therapy, on the first day and after 1 week of treatment.


METHODS
Data from four patients with systemic PUVA and seven patients with bath PUVA were available (age range 23-71 years, five women and six men).


RESULTS
For all of the patients, individual pre-PUVA caffeine clearance values were above the lower limit of previously assessed reference ranges. Systemic PUVA markedly decreased caffeine clearance by factors of 0.17 [90% confidence interval (CI) 0.07-0.42] on the first day and 0.14 (90% CI 0.05-0.36) after 1 week of treatment, respectively, and values thus dropped below the reference ranges. In contrast, bath PUVA had no obvious effect on pre-PUVA clearance values as the latter changed by factors of 1.00 (90% CI 0.81-1.23) and 1.05 (90% CI 0.75-1.49) on the first day and after 1 week of treatment, respectively.


CONCLUSIONS
Systemic PUVA causes pronounced inhibition of liver CYP1A2, while bath PUVA has no such effect. The extent of interaction makes a dose adjustment for most CYP1A2 substrates such as theophylline mandatory in patients undergoing systemic PUVA.
Tantcheva-Poór
I
I
Institute for Pharmacology, Clinical Pharmacology, 50931 Köln, Germany.
Servera-Llaneras
M
M
Scharffetter-Kochanek
K
K
Fuhr
U
U
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001494:Baths; D002110:Caffeine / Q000493:pharmacokinetics; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008297:Male; D008730:Methoxsalen / Q000008:administration & dosage; D008875:Middle Aged; D011701:PUVA Therapy / Q000379:methods; D012871:Skin Diseases / Q000188:drug therapy / Q000201:enzymology*
D065609:Cytochrome P-450 CYP1A2 Inhibitors; D002110:Caffeine; D019388:Cytochrome P-450 CYP1A2; D008730:Methoxsalen