Timing of 5-aminolaevulinic acid-induced photodynamic therapy for the treatment of patients with Barrett's oesophagus.
5-Aminolaevulinic acid-induced photodynamic therapy (ALA-PDT) is being used as an experimental treatment of Barrett's oesophagus (BE), a pre-malignant disorder in the distal oesophagus. The present study aims to acquire detailed knowledge on the pharmacokinetics of ALA and the photosensitizer protoporphyin IX (PPIX) in tissues and plasma of patients with BE to provide a rationale for the conditions used in ALA-PDT. A total of 26 patients with BE were randomized to varying time intervals between ingesting 60 mg/kg ALA and undergoing an endoscopy with biopsies of BE, normal oesophageal and gastric mucosa. At 1, 2, 7, 8 and 24 h, two patients at each time, and at 3, 4, 5 and 6 h, four patients at each time after ALA ingestion were included. ALA, porphyrin intermediates and PPIX were determined in all biopsy and plasma samples. The maximum concentration of PPIX was found earlier in BE (4.6+/-0.5 h) than in squamous epithelium (SQ) (6.6+/-2.2 h) (P<0.05). PPIX concentrations were higher in SQ than in BE especially at longer time intervals. In addition, tissue ALA concentrations were found to be 20-fold higher than the plasma concentrations at 1 h after ALA ingestion, suggesting uptake from the oesophageal lumen. Skin photosensitivity was short-lasting but often debilitating. Our results provide a rationale for the use of ALA-PDT for the treatment of BE at 4-5 h after ALA ingestion and for local application of ALA in the oesophagus. Patients undergoing ALA-PDT must be strongly advised to avoid sunlight for at least 24-36 h.
Department of Internal Medicine, Erasmus MC, University Medical Center, Dr Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
Petra
P
Hinnen
Felix W M
FW
de Rooij
Wim C J
WC
Hop
Annie
A
Edixhoven
Herman
H
van Dekken
J H Paul
JH
Wilson
Peter D
PD
Siersema
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001471:Barrett Esophagus / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D001706:Biopsy; D004724:Endoscopy; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009092:Mucous Membrane / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D011524:Protoporphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D012016:Reference Values; D014018:Tissue Distribution
D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX