Blackwell Publishing Journal Backfiles 1879-2005
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. Objectives 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.
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