Pharmacokinetics of 8-methoxypsoralen during extracorporeal photopheresis

Abstract

Background/purpose: Extracorporeal photopheresis (ECP) is a widely used therapy for the treatment of diverse diseases such as cutaneous lymphomas and graft-vs-host disease. Knowledge of the effective concentration of 8-methoxypsoralen (8-MOP) in the photopheresis apparatus and the photodegradation time-course of 8-MOP during ECP is a prerequisite for a successful therapy.

Methods: The time course of 8-MOP concentration was measured in patients' serum and in the photoactivation chamber (so-called buffy coat fraction) during ECP. Samples were analyzed by high-performance liquid chromatography. Half-lives of 8-MOP in both fractions were calculated assuming first-order kinetics (exponential decay). Losses due to adsorption and photodegradation were investigated and the recovery of bioavailable 8-MOP calculated.

Results: In female patients (average age 61+/-9 years) given 0.4-0.6 mg 8-MOP/kg body weight in the form of Oxsoralen capsules, peak serum concentrations averaged 420+/-80 ng/ml (n=8). In contrast, peak concentrations in the photoactivation chamber averaged only 134 ng/ml, or 32% of serum values. In serum, peak 8-MOP concentrations were reached < or =40 min following ingestion; the half-life of 8-MOP in the serum was 50+/-14 min (n=7). The effective half-life of 8-MOP in the photoactivation chamber was considerably longer (about 4 h). The recovery of free, bioavailable 8-MOP in the photoactivation chamber at the end of ECP averaged 42% of the applied dose; losses stemmed mainly from photodegradation of 8-MOP and from adsorption of 8-MOP to the surfaces of the apparatus.

Conclusion: We conclude that interpretation of investigations on clinical success and dose-response aspects of ECP must take into account the complex pharmacokinetic behaviour of 8-MOP during the ECP procedure.