Intraindividual and interindividual variability in 8-methoxypsoralen kinetics and effect in psoriatic patients

Our purpose was to investigate the origin of intraindividual variation in comparison with interindividual variation of 8-methoxypsoralen (8-MOP) kinetics in different body fluids. The clinical test in therapy with psoralens and ultraviolet A (PUVA), expressed as the minimal phototoxic dose (MPD), was performed to establish a possible connection between biologic effect and kinetics of 8-MOP. The MPD and 8-MOP kinetics in serum and suction blister fluid (sbf) were determined in 18 psoriatic patients on PUVA therapy in 4 test days spread over a 7-mo period. Evidence showed that interindividual fluctuations are caused by differences in intrinsic clearance (Cl). Interindividual variations are large in comparison with intraindividual variations. A correlation was found among maximal serum concentrations, Cls, MPDs, and concentrations in sbf. In clinical practice the maximal serum concentration, determined in blood samples taken at 1, 2, and 3 hr after 8-MOP ingestion, is indicative of the rate of 8-MOP metabolism and thus of the biologic effect in the patient.