Liver cytochrome P450 CYP1A2 is markedly inhibited by systemic but not by bath PUVA in dermatological patients

Br J Dermatol. 2001 Jun;144(6):1127-32. doi: 10.1046/j.1365-2133.2001.04233.x.


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.

MeSH terms

  • Administration, Cutaneous
  • Administration, Oral
  • Adult
  • Aged
  • Baths
  • Caffeine / pharmacokinetics
  • Cytochrome P-450 CYP1A2 / metabolism
  • Cytochrome P-450 CYP1A2 Inhibitors*
  • Female
  • Humans
  • Liver / enzymology*
  • Male
  • Methoxsalen / administration & dosage
  • Middle Aged
  • PUVA Therapy* / methods
  • Skin Diseases / drug therapy
  • Skin Diseases / enzymology*


  • Cytochrome P-450 CYP1A2 Inhibitors
  • Caffeine
  • Cytochrome P-450 CYP1A2
  • Methoxsalen