Pharmacokinetics of 8-methoxypsoralen during extracorporeal photopheresis

Détails

ID Serval
serval:BIB_2218F039FE46
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Pharmacokinetics of 8-methoxypsoralen during extracorporeal photopheresis
Périodique
Photodermatology, Photoimmunology and Photomedicine
Auteur(s)
Shephard  S. E., Nestle  F. O., Panizzon  R.
ISSN
0905-4383 (Print)
Statut éditorial
Publié
Date de publication
04/1999
Volume
15
Numéro
2
Pages
64-74
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Apr
Résumé
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.
Mots-clé
Adult Aged Biological Availability Chromatography, High Pressure Liquid Dose-Response Relationship, Drug Female Graft vs Host Disease/drug therapy/*metabolism Humans Lymphoma, T-Cell, Cutaneous/drug therapy/*metabolism Methoxsalen/administration & dosage/blood/*pharmacokinetics Middle Aged *Photopheresis Photosensitizing Agents/administration & dosage/blood/*pharmacokinetics Skin Neoplasms/drug therapy/*metabolism
Pubmed
Web of science
Création de la notice
25/01/2008 16:55
Dernière modification de la notice
20/08/2019 12:59
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