Phototoxic reactions in healthy volunteers following photodynamic therapy with methylaminolevulinate cream or with cream containing 5-aminolevulinic acid: a phase II, randomized study.

BACKGROUND: Photodynamic therapy (PDT) is the selective destruction of abnormal cells through activation of a photosensitizer in the presence of oxygen. Local phototoxic reactions and pain are the most common limiting side effects. PURPOSE: The primary objective was to compare the local phototoxic response following PDT with methylaminolevulinate (MAL) and 5-aminolevulinic acid (ALA). The secondary objectives were to compare the two treatments regarding pain, detection of substance P, change in fluorescence intensity from before to 5 h after cream application and adverse events not related to local phototoxicity. METHODS: Thirty-four healthy volunteers were treated by PDT using MAL 160 mg/g cream and ALA cream 20% randomly assigned to treatment areas on the inside of each upper arm. A composite score of local phototoxic events (erythema, edema, hyperpigmentation) was calculated. RESULTS: The area under the curve (AUC) analysis of composite scores showed a significantly higher AUC for ALA-PDT (P < or =0.0001). ALA- and MAL-PDT showed equivalent local side-effect frequencies, except for a higher frequency of hyperpigmentation after 28 d using ALA-PDT (P=0.006). CONCLUSION: MAL- and ALA-PDT are nearly equivalent regarding individual side-effect frequencies, but MAL-PDT has a more favorable phototoxicity pattern as seen by AUC analysis and the lower frequency of long-lasting hyperpigmentation.

Fluorescence characteristics and pharmacokinetic properties of a novel self-adhesive 5-ALA patch for photodynamic therapy of actinic keratoses.

Actinic keratosis (AK) can be treated by photodynamic therapy (PDT), which is becoming a well-established tool in dermatology. Normally a precursor of the photosensitiser is applied topically and converted into protoporphyrin IX (PPIX) in the cells. By activating PPIX with light, the dysplastic cells will be destroyed. We report the results of two clinical studies investigating the properties of a novel self-adhesive 5-ALA-patch (PD P 506 A) intended for PDT of mild to moderate AK on the face and head. The studies investigated the influence of patch application duration on PPIX-specific fluorescence and the pharmacokinetic properties of the 5-ALA patch. The PPIX fluorescence in AK lesions and normal skin after patch application (intraindividual comparison; application for 2, 3, 4, 5 h) was investigated in 13 patients using DYADERM Professional (Biocam). In the subsequent pharmacokinetic study 12 patients were treated with 8 patches each (4 h application). 5-ALA and PPIX were analysed in plasma (over 24 h) and urine (over 12 h). PPIX-specific fluorescence measured immediately after patch removal increased with increasing application duration to a maximum at 4-h application. The fluorescence in AK lesions was more intense than in normal skin. A small increase of 5-ALA plasma concentrations was observed in 10 of 12 patients after applying 8 patches for 4 h, which rapidly declined to normal values after patch removal. The maximum increase was 3.7-fold of the pre-dose 5-ALA plasma concentration. No PPIX-concentrations above the lower limit of quantification were observed. PPIX-specific fluorescence in AK lesions can be steered by application duration of this novel 5-ALA patch. Application is safe and well tolerable. The observed small rise in 5-ALA plasma concentrations is regarded clinically irrelevant. Clinical efficacy of the patch in PDT will be investigated in further clinical trials.