Pharmacokinetics of 5-aminolevulinic acid-induced protoporphyrin IX in skin and blood

Rick, K.; Sroka, Ronald; Stepp, Herbert; Kriegmair, M.; Huber, Rudolf M.; Jacob, K.; Baumgartner, Reinhold

doi:10.1016/s1011-1344(97)00076-6

Cited by 119 publications

(79 citation statements)

References 23 publications

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“…The fluorescence peak time and intensity was reported to vary for different body parts which might explain why no fluorescence could be detected in the skin of the foot instep of one patient in the higher dose group [22]. No data is available for the peak time in human brain tumor due to the restrictions of the surgical circumstances.…”

Section: Discussionmentioning

confidence: 99%

Low dose 5-aminolevulinic acid: Implications in spectroscopic measurements during brain tumor surgery

Haj‐Hosseini

Richter

Hallbeck

et al. 2015

Photodiagnosis and Photodynamic Therapy

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Section: Discussionmentioning

confidence: 99%

Low dose 5-aminolevulinic acid: Implications in spectroscopic measurements during brain tumor surgery

Haj‐Hosseini

Richter

Hallbeck

et al. 2015

Photodiagnosis and Photodynamic Therapy

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“…In addition, its topical administration in the treatment of non-melanoma skin cancer in comparison to systemic application can be more efficient, since higher local concentrations in the cancerous tissue can be obtained (Rick et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Fluorometric quantification of protoporphyrin IX in biological skin samples from in vitro penetration/permeation studies

Rossetti

Depieri

Tedesco

et al. 2010

Braz. J. Pharm. Sci.

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A fluorometric analytical method was developed for quantification of protoporphyrin IX (PpIX) in skin samples and receptor phase solution after in vitro cutaneous penetration/permeation studies. Analytical conditions used were: excitation and emission wavelengths: 400 nm and 632 nm; bandwidth: 0.5 nm; excitation and emission slits: 10/10. PpIX was recovered from two different layers of skin, the stratum corneum (SC) and the epidermis plus dermis ([E+D]), by vortex homogenization, probe and bath sonication, using DMSO as an extraction solvent. The detection and quantification limits were 0.002 and 0.005 µg/mL, respectively. The assay was linear from 0.005 -0.5 µg/mL. The within-day and betweenday assay precision and accuracy in DMSO and receptor phase solution were each studied at the two concentration levels 0.04 and 0.2 µg/mL, and 0.01 and 0.08 µg/mL, respectively. The coefficients of variation and deviation from the theoretical values were lower than 5%. The skin recovery of PpIX from SC and [E+D] layers using two different concentrations (0.5 and 1.0 µg/mL) were all above 90.0%. The method described has potential application to in vitro penetration/permeation studies of PpIX using porcine skin as a biological membrane model. Uniterms: Fluorometric quantification. Protoporphyrin IX/determination. Photodynamic therapy. Porcine skin. Cutaneous penetration/in vitro study. Cutaneous permeation/in vitro study.Um método analítico por espectrofluorimetria foi desenvolvido para quantificar a protoporfirina IX (Pp IX) em amostras de pele e fase receptora após a realização de testes in vitro de penetração/permeação cutâneas. As condições analíticas utilizadas foram: comprimentos de onda de excitação e emissão: 400 nm e 632 nm; largura de banda: 0,5 nm; fendas de excitação e emissão: 10/10. A PpIX foi extraída de amostras de estrato córneo (EC) e da epiderme sem estrato córneo + derme ([E+D]) através da agitação em vórtex e sonicação por haste e banho, utilizando-se o DMSO como solvente extrator. O limite de detecção e quantificação foram, respectivamente, de 0,002 e 0,005 µg/mL. O método mostrou-se linear da faixa de 0,005 -0,5 µg/mL. A precisão e exatidão intra e inter-ensaio em DMSO e na fase receptora foram validadas utilizando-se duas concentrações distintas, respectivamente, de 0,004 e 0,2 µg/mL, e 0,01 e 0,08 µg/mL. Os valores de coeficiente de variação e o desvio do valor teórico foram inferiores a 5%. A recuperação da PpIX das camadas da pele (EC e [E+D]) utilizando-se duas concentrações distintas (0,5 e 1,0 µg/mL) foram todas acima de 90,0%. O método descrito pode ser utilizado para determinação da PpIX após estudos de penetração/permeação cutânea in vitro utilizando pele de porco como modelo de membrana.Unitermos: Espectrofluorimetria/análise quantitativa. Quantificação fluorimétrica. Protoporfirina IX/ determinação. Terapia fotodinâmica. Pele porcina. Penetração cutânea/estudo in vitro. Permeação cutânea/estudo in vitro.

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“…Although the photosensitising drug Photofrin-II 1 has received regulatory approval for use in a number of conditions (Dougherty et al, 1998), patients often have to be limited to subdued lighting for several weeks following treatment due to its prolonged retention in the skin (Carruth, 1998). In contrast, skin photosensitivity following the systemic administration of 5-aminolaevulinic acid (ALA), a metabolic precursor of the photosensitiser protoporphyrin-IX (PpIX), is relatively mild and short-lived (Rick et al, 1997). ALA-based PDT is now being investigated as a treatment for several conditions Peng et al, 1997b).…”

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confidence: 99%

Porphyrin accumulation induced by 5-aminolaevulinic acid esters in tumour cells growing in vitro and in vivo

et al. 2002

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The ability of 5-aminolaevulinic acid and some of its esterified derivatives to induce porphyrin accumulation has been examined in CaNT murine mammary carcinoma cells growing in culture and as tumours in vivo. Topical or intravenous administration of 5-aminolaevulinic acid-esters to mice bearing subcutaneous tumours produced lower porphyrin levels in the tumour than an equimolar dose of 5-aminolaevulinic acid. Reducing the dose of intravenous hexyl-or benzyl-ALA and topical hexyl-5-aminolaevulinic acid resulted in a dose-dependent reduction in porphyrin accumulation. A number of normal tissues accumulated higher concentrations of porphyrins than tumour tissue following intravenous administration of 5-aminolaevulinic acid-esters. Esterase activity in these normal tissues was greater than that in tumour tissue. In contrast to the situation in vivo, all of the 5-aminolaevulinic acid-esters examined were at least as effective as 5-aminolaevulinic acid when applied to cloned CaNT cells in vitro, with the drug concentration required for maximum porphyrin accumulation varying with ester chain-length. Tumour cells growing in culture released esterase activity into the medium. These findings suggest that the efficacy of 5-aminolaevulinic esters may vary depending on the esterase activity of the target tissue, and suggest caution when interpreting the findings of in vitro studies using these and similar prodrugs.

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Pharmacokinetics of 5-aminolevulinic acid-induced protoporphyrin IX in skin and blood

Cited by 119 publications

References 23 publications

Low dose 5-aminolevulinic acid: Implications in spectroscopic measurements during brain tumor surgery

Low dose 5-aminolevulinic acid: Implications in spectroscopic measurements during brain tumor surgery

Fluorometric quantification of protoporphyrin IX in biological skin samples from in vitro penetration/permeation studies

Porphyrin accumulation induced by 5-aminolaevulinic acid esters in tumour cells growing in vitro and in vivo

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