Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0349506 (photosensitivity)
 4,145 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Photodynamic therapy (PDT) involves the sequential administration of photosensitizing drugs and light for the treatment of diseased tissue. The first photosensitizer systematically evaluated for PDT was hematoporphyrin derivative (HPD). Porfimer sodium (Photofrin; manufactured by Lederle Parenterals, Carolina, Puerto Rico, under license from Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada) is a chemically related photosensitizing agent. Preliminary trials suggest a role for PDT in the treatment of primary, recurrent, and metastatic nonmelanoma skin cancers. Both HPD and porfimer sodium appear to be limited by generalized cutaneous photosensitivity, which lasts up to 6 to 8 weeks after administration. Benzoporphyrin derivative (BPD verteporfin; BPD-Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada) is a second-generation porphyrin that has shown promise in clinical studies as a safe and effective photosensitizer for PDT of non-melanoma cutaneous malignancies. Benzoporphyrin derivative is activated by a longer, more penetrating wavelength of light than is porfimer sodium, and has a shorter duration of cutaneous photosensitivity following systemic administration. The use of BPD for PDT of nononcologic conditions also had been studied. Recent trials have shown efficacy in the treatment of psoriasis by BPD-sensitized PDT using drug and light doses lower than those used for malignant tumors.
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PMID:Photodynamic therapy in dermatology with porfimer sodium and benzoporphyrin derivative: an update. 799 1

Photodynamic therapy (PDT) is based on the use of light-sensitive molecules called photosensitizers. Photoactivation causes the formation of singlet oxygen, which produces peroxidative reactions that can cause cell damage and death. Porfimer sodium (Photofrin, manufactured by Lederle Parenterals, Carolina, Puerto Rico, under license from Quadra Logic Technologies, Inc, Vancouver, BC, Canada) is the photosensitizer that has been studied most extensively. Patients generally have to be hospitalized for 2 days prior to light treatment after administration of porfimer sodium; it takes approximately 48 hours after injection to reach optimal concentration in tumor tissue. The tumoricidal capacity of PDT with porfimer sodium is determined in part by the maximum depth of penetration of light having a wavelength of 630 nm. Porfimer sodium causes cutaneous photosensitivity that may last for up to 6 weeks. Benzoporphyrin derivative (BPD verteporfin; BPD-Quadra Logic Technologies, Inc, Vancouver, BC, Canada), another photosensitizer, accumulates more rapidly in tumor tissue, permitting optimal PDT 30 to 150 minutes following intravenous administration. It is rapidly cleared from the body, and skin photosensitivity does not extend beyond a few days. The primary mechanism of action of PDT is related to the selective accumulation of photosensitizers in cancer tissue. Photodynamic therapy also shows promise in the treatment of a number of nonneoplastic conditions, including psoriasis, macular degeneration of the retina, atherosclerotic plaque and restenosis, bone marrow purging for treatment of leukemias with autologous bone marrow transplantation, inactivation of viruses in blood or blood products, and several autoimmune conditions, including rheumatoid arthritis. Physiologic characteristics shared by this disparate group of diseases, and the mechanisms by which they may mediate photoactivation, are discussed.
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PMID:Photosensitizers in photodynamic therapy. 799 5

Verteporfin, a benzoporphyrin derivative monoacid ring A, is a photosensitising drug for photodynamic therapy (PDT) activated by low-intensity, nonheat-generating light of 689nm wavelength. Activation generates cytotoxic oxygen free radicals. The specificity and uptake of verteporfin for target cells with a high expression of low density lipoprotein (LDL) receptors, such as tumour and neovascular endothelial cells, is enhanced by the use of a liposomal formulation and its rapid uptake by plasma LDL. Verteporfin therapy (at light doses < 150 J/cm) selectively damages neovascular endothelial cells leading to thrombus formation and specific occlusion of choroidal neovascular vessels in subfoveal lesions in patients with age-related macular degeneration (AMD). Repeated applications of verteporfin therapy 6 mg/m2 improved or maintained visual acuity in the majority of patients with some classic subfoveal choroidal neovascularisation (CNV) secondary to AMD at 1 year's follow-up in 2 large multicentre, placebo-controlled, double-blind trials. Furthermore. in a subgroup of these patients with predominantly classic CNV secondary to AMD, there was a significantly more marked visual acuity (VA) benefit with 67.3% of verteporfin-treated eyes experiencing less than a 15-letter loss of VA versus 39.3% with placebo treatment. Multiple applications of verteporfin therapy were well tolerated in patients with subfoveal CNV secondary to AMD. The most common adverse events were visual disturbances, injection site reactions, photosensitivity reactions and infusion-related back pain.
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PMID:Verteporfin. 1075 29

(1) The reference treatment for neovascular forms of age-related macular degeneration is laser coagulation of the neovessels, but it is not applicable to subfoveal lesions. (2) Verteporfin, a photosensitising agent, is injected 15 minutes before red laser therapy in patients with neovascularisation predominantly visible in the subfoveal choroidial region. (3) The clinical file mainly comprises two double-blind placebo-controlled trials with identical designs, in which verteporfin was injected before laser therapy. These trials show that verteporfin-laser combination therapy sometimes improves visual acuity (16% of eyes, versus 7% with laser therapy alone). It also moderately reduces the loss of vision measured at 2 years: 53% of patients have a limited loss, compared with 38% of patients treated with laser alone. The impact of this difference on daily life activities is not known. (4) A retrospective subgroup analysis suggests that only patients with predominantly visible neovascularisation benefit from treatment with verteporfin. (5) The main adverse effects of verteporfin are visual. Prolonged reduction in visual acuity has mainly been reported in patients with occult neovascularisation. The main systemic risk is of photosensitivity reactions, and precautions must be taken for 48 hours following treatment. (6) In practice, only patients with subfoveal neovessels are likely to benefit from red laser + verteporfin combination therapy. (7) Verteporfin therapy is very expensive.
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PMID:Verteporfin: new preparation. In combination with laser therapy: helpful in some forms of age-related macular degeneration. 1171 69

Verteporfin, a benzoporphyrin derivative, is the first photo-sensitive (light-activated) drug to be proven effective in treating certain types of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The pharmacokinetics of light-activated drugs are central to their safety and efficacy. Forty healthy Caucasian volunteers, 24 healthy Japanese volunteers, 9 patients with mild hepatic dysfunction, 69 patients with CNV due to AMD, and 21 patients with skin cancer were infused with verteporfin 3 to 20 mg/m2 of body surface area over 1.5 to 45 minutes. Verteporfin regioisomers and the metabolite benzoporphyrin derivative diacid (BPD-DA) were quantified by validated methods of liquid chromatography and capillary electrophoresis with laser-induced fluorescence. Cmax of verteporfin occurred at the end of the infusion and was proportional to the dose and rate of infusion. The extent of formation of the metabolite BPD-DA was less than 10%, based on the AUC ratio. Renal elimination was minimal (< 0.01% of the dose). All groups studied had similar pharmacokinetics, which were biexponential with distribution in the first 1 to 3 hours and elimination t(1/2) of 5 to 6 hours. No significant differences were observed between Japanese and Caucasian volunteers or between men and women. Patients older than 65 years had a slightly higher average Cmax than patients younger than 65 years (1.14 vs. 1.03 microg/ml, p = 0.066), but the ranges of the two age groups overlapped. Verteporfin has a short half-life and is rapidly eliminated in the bile, mainly as unchanged drug. Based on pharmacokinetic data, dose adjustments are not required for age, gender, race, or mild hepatic or renal impairment. The rapid elimination of verteporfin shows that the period of skin photosensitivity is unlikely to persist after 24 to 48 hours.
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PMID:Clinical pharmacokinetics of verteporfin. 1201 49

Photodynamic therapy with Verteporfin, a potent photosensitizer dye, is a very effective treatment for age related macular degeneration due to choroidal neovascularization. Photodynamic therapy offers the potential for selective tissue injury in part attributable to preferential localization of Verteporfin, administrated by intravenous infusion, to the choroidal neovascularization complex and irradiation of the complex with non-laser thermal light at 690 nm resulting in at least temporary thrombosis and vessel closure. Verteporfin is a benzoporphyrin derivative monoacid ring A formulated as a unilamellar liposome. In the blood Verteporfin is associated with lipoprotein fractions and is rapidly cleared via a receptor-mediated uptake mechanism due the high expression of LDL receptors in neovascular tissues. Verteporfin was undetectable in plasma 24 hr after infusion of the recommended dose: 6 mg/m2 of body surface area. The main side effect is photosensitivity of skin which is usually short-lived (24-48 hr) with a low incidence (2.3%). As skin photosensitivity depends on circulating rather than tissue drug levels, we investigate the possibility of developing a simple, fast and reliable spectrofluorometric method to measure plasma Verteporfin levels. Fluorescence emission spectrum (550-750 nm) of 1:10 saline diluted plasma with lambda exc=430 nm showed a characteristic emission peak at 692 nm, the height being proportional to the Verteporfin levels. The sensitivity is around 100 ng/ml and the pharmacokinetics of Verteporfin has been studied from 0 to 5 hr after infusion in six patients older than 65 years with age-related macular degeneration.
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PMID:Simple, reliable and fast spectrofluorometric method for determination of plasma Verteporfin (Visudyne) levels during photodynamic therapy for choroidal neovascularization. 1269 52

Photodynamic therapy (PDT) is a novel treatment entity that exploits the photophysical properties of various photosensitive chemical entities which, upon light activation, results in targeted photooxidation and subsequent tissue destruction. The antiangiogenic properties of PDT have been adapted for treatment of subfoveal choroidal neovascular membranes due to disease states such as age-related macular degeneration (AMD). Historically, PDT has been limited by a lack of suitable photosensitive dyes. However, agents such as verteporfin, a second-generation benzoporphyrin derivative, appear to be free from the extensive phototoxicity that limited the success of previous agents. Verteporfin has a high affinity for choroidal neovascular membranes, typically found with exudative AMD, and upon photoactivation results in targeted microvascular damage and thrombus formation with resultant vessel occlusion. Scrutiny of diagnostic indicators for verteporfin administration, including critical angiographic evaluation of lesion size and visual acuity, is essential to treatment success. Large lesions with relatively good visual acuity (20/50 or better) may be at particular risk for marked vision loss following verteporfin administration. Lesion composition also appears to influence visual outcome with verteporfin use. The safety of verteporfin is directly dependent upon the appropriate integration of dosage, infusion and light activation required for a suitable pharmacotherapeutic outcome. When used appropriately, and with adequate patient education regarding photosensitivity, the risk-benefit of verteporfin for the medical treatment of neovascular AMD is favourable.
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PMID:Safety of verteporfin for treatment of subfoveal choroidal neovascular membranes associated with age-related macular degeneration. 1526 51

Photodynamic therapy (PDT) is a form of photochemotherapy requiring the simultaneous presence of a photosensitiser, activating light of the proper wavelength and molecular oxygen in order to produce a localised therapeutic effect thought to be due to high-energy singlet oxygen generation. Neither drug nor light alone are effective as therapeutic agents and thus PDT treatment methods should be looked upon as true, necessary, drug and device combinations ('systems'). Selectivity of treatment is imparted by a combination of factors, including accumulation of photosensitiser by the target lesion and targeted application of activating light. The most common systemic side effect of systemically administered photosensitisers is cutaneous photosensitivity of varying periods of time. Local toxicities depend on the area of treatment. Sources of light which have been used in PDT include lasers, arc lamps, light-emitting diodes and fluorescent lamps. PDT has been used for a wide variety of clinical applications. In 1995, the first PDT system, using porfimer sodium (Photofrin, Axcan Pharma, Inc.), lasers and fibre optic light delivery methods, developed by QuadraLogic Technologies, was approved in the US for endoscopic palliation of malignant dysphagia caused by oesophageal cancer. A topical PDT system, aminolevulinic acid HCL (Levulan Kerastick) and the large-area BLU-U PDT Illuminator, was developed by DUSA Pharmaceuticals, Inc. for the treatment of actinic keratoses of the face and scalp and approved in the US in 2000. Topical PDT has applicability to a wide variety of skin cancers and precancerous conditions. In 2001, Novartis launched the systemically administered verteporfin (Visudyne) laser-based PDT system in the US as the first pharmacologic treatment for age-related macular degeneration. Development programmes are continuing to investigate PDT for the potential treatment of a variety of diseases, yielding therapeutic results with minimal toxicity.
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PMID:Photodynamic therapy systems and applications. 1598 54

We report the synthesis, spectroscopic properties and intracellular imaging of recombinant antibody single chain fragment (scFv) conjugates with photosensitizers used for photodynamic therapy of cancer (PDT). Two widely-studied photosensitizers have been selected: preclinical pyropheophorbide-a (PPa) and verteporfin (VP), which has been clinically approved for the treatment of acute macular degeneration (Visudyne). Pyropheophorbide-a and verteporfin have been conjugated to an anti-HER2 scFv containing on average ten photosensitizer molecules per scFv with a small contribution (<or=20%) from non-covalently bound molecules. Confocal fluorescence microscopy demonstrates good cellular uptake of PPa conjugate with the HER2-positive cell line, SKOV-3, while negligible cell uptake is demonstrated for the HER2-negative cell line, KB. For the VP conjugate, increased rate of cellular uptake and prolonged retention in SKOV-3 cells is observed compared to free photosensitizer. In clinical applications this could provide increased potency and desired selectivity towards malignant tissue, leaving surrounding healthy tissue unharmed and reducing skin photosensitivity. The present study highlights the usefulness of photosensitizer immunoconjugates with scFvs for targeted PDT.
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PMID:Fluorescence characterisation of multiply-loaded anti-HER2 single chain Fv-photosensitizer conjugates suitable for photodynamic therapy. 1772 91

Photodynamic therapy (PDT) of skin tumors or pre-cancerous lesions and of age-related macular degeneration combines the administration of porphyrins or porphyrin precursors and illumination with red light at the diseased sites. Photosensitizers absorbing light beyond 630 nm where tissues have the highest transmittance produce singlet oxygen, a highly reactive activated oxygen species and a major cytotoxin. The PDT of age-related macular degeneration is performed with red laser light after i.v. injection of verteporfin (Visudyne) a hydrophobic porphyrin carried by serum lipoproteins whose endocytosis leads to accumulation of the porphyrin in endothelial cells of choroidal neo-vessels. In the PDT of skin cancers, local synthesis of the photosensitizer occurs after topical application of the natural protoporphyrin IX precursor delta-aminolevulinic acid (or its ester forms) on the lesions. In all the cases, the photosensitizers should be rapidly excreted to avoid a long lasting skin photosensitivity.
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PMID:Photodynamic therapy: Dermatology and ophthalmology as main fields of current applications in clinic. 1906 42


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