Drug‐Drug Interaction After Single Oral Doses of the Furanocoumarin Methoxsalen and Cyclosporine

Abstract

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 (Cmax) 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.

Herb-drug Interactions in Neuropsychiatric Pharmacotherapy – A Review of Clinically Relevant Findings

“…Phytoestrogens and other bioactive components of celery can interact with the DMEs, including those in the CYP450 family. Potent inhibition of the several isoforms of CYP by celery extracts, including active components like methoxsalen, has been reported [ 48 - 50 ]. In animal studies, celery extracts inhibit the metabolism and prolong the effects of CYP substrates [ 51 , 52 ].…”

Selective Inhibitory Effect of Osthenol on Human Cytochrome 2C8

“…In addition, 8‐methoxypsoralen (methoxsalen), a naturally occurring furanocoumarin with photosensitizing properties, was demonstrated to have a clinically significant interaction with cyclosporine by potently inhibiting CYP3A4 . Moreover, marmelosin, a furanocoumarin isolated from Aegle marmelos , reversibly and non‐competitively inhibited CYP1A2 …”