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

Abstract

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.

Optimization of photodynamic therapy with a novel self-adhesive 5-aminolaevulinic acid patch: results of two randomized controlled phase III studies

“…This led to the development of the thin 5‐ALA patch, PD P 506 A. A fluorescence analysis had shown that the PpIX content in AK lesions is dependent on the application duration 8 . This finding was verified in a clinical dose‐finding study which defined the 4 h application of the 5‐ALA patch as optimal 9 .…”

“…A long incubation interval of the alcoholic solution, the need for ablation of scales and crusts prior to cream application and light protection after cream application with an occlusive and light‐tight dressing make the procedure time consuming and complex for both patient and physician. In order to facilitate PDT and to shorten handling times, a self‐adhesive, skin‐coloured thin 5‐ALA patch (product code PD P 506 A) was developed 8 . As the 5‐ALA patch is intended to be applied directly to AK lesions, crust removal prior to application is not necessary.…”

“…The optimum application duration of the 5‐ALA patch to mild to moderate 2 AK lesions of head and face has been investigated in two preceding studies. A fluorescence analysis study assessed the influence of patch application duration on the protoporphyrin IX (PpIX)‐specific fluorescence in AK lesions 8 . It was shown that PpIX‐specific fluorescence immediately after patch removal increased with increasing application duration to a maximum at 4 h application.…”

Monitoring the accumulation and dissipation of the photosensitizer protoporphyrin IX during standard dermatological methyl-aminolevulinate photodynamic therapy utilizing non-invasive fluorescence imaging and quantification

“…This invasive technique does not enable the photosensitizer to be followed during realtime, it simply provides information about PpIX concentration at one specific point following the process being terminated. The non-invasive commercially available imaging system employed within this study (Dyaderm, Biocam, Germany) is utilized by several groups for photodiagnosis of skin lesions (28,29). Following extensive validation, this system was considered to be capable of monitoring changes in PpIX during real-time MAL-PDT (30).…”

Photodynamic therapy simplified: nonprepared, moderate-grade actinic keratosis lesions respond equally well to 5-aminolaevulinic acid patch photodynamic therapy as do mild lesions

“…The 5‐ALA patch formulation was applied to mild‐ and moderate‐grade AK lesions in clinical trials without pretreatment of the lesions . AK lesion grades were defined according to Cockerell, which do include hyperkeratosis for moderate lesions, as opposed to the definition of Olsen et al …”