Chronopharmacokinetics of 5-methoxypsoralen.

Abstract

Diurnal variations in drug pharmacokinetics are a well known phenomenon. Chronopharmacology studies now appear to be attracting increasing interest with a view to establishing an optimum therapeutic prescription. In order to determine possible chronobiological variations of 5-methoxypsoralen (5-MOP) pharmacokinetic, 5-MOP blood concentrations were quantified in 8 healthy subjects after drug ingestion at different times during the day. Stolk's High Performance Liquid Chromatography technique was used to assess the 5-MOP serum concentrations. Each subject underwent three pharmacokinetic studies after oral ingestion of 5-MOP (1.2 mg/kg), in conjunction with a standardized low-lipid meal. The first pharmacokinetic study was started in the morning, the second in the afternoon and the third in the evening. Drug intake was at intervals of 2 days, to avoid drug accumulation. The results showed that the evening intake of the drug induced a higher 5-MOP maximum concentration and a higher 'area under curve' than morning or afternoon ingestion. This study suggests an optimized PUVA therapy, when performed in the evening.