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Drug‐Drug Interaction After Single Oral Doses of the Furanocoumarin Methoxsalen and Cyclosporine
Author(s) -
Rheeders Malie,
Bouwer Marlène,
Goosen Theunis C.
Publication year - 2006
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270006288732
Subject(s) - furanocoumarin , methoxsalen , drug , pharmacology , medicine , dermatology , chemistry , organic chemistry , psoriasis
Furanocoumarins increase the bioavailability of drugs that are CYP3A4 substrates. A possible interaction of methoxsalen with cyclosporine was evaluated in 12 healthy volunteers following oral administration of 40 mg methoxsalen, 200 mg cyclosporine, or a combination of both in a randomized crossover study. Methoxsalen increased area under the plasma concentration‐time curve (AUC) and peak plasma concentration (C max ) of cyclosporine by 29% (range, −20% to 172%; P <.05) and 8% (range, −10% to 26%; P < .05), respectively, compared to cyclosporine alone. The AUC geometric means ratio (95% confidence interval) for cyclosporine plus methoxsalen/cyclosporine alone was 1.14 (1.02, 1.27), and treatments were therefore not bioequivalent. Methoxsalen causes a clinically significant interaction with cyclosporine in some susceptible individuals. The reasons for susceptibility and the clinical implications for chronic cyclosporine administration have not been established. Caution is recommended in combination therapy, and more frequent monitoring of cyclosporine plasma levels and clinical monitoring is advised.