Retinoids in dermatology: an interim report

Peck, Gary L.

doi:10.1001/archderm.116.3.283

Cited by 13 publications

(8 citation statements)

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“…The introduction of isotretinoin and etretinatc has been a major advance in dermatotherapy. Isotretinoin (Roaccutane'), in doses of 05-2 mg/kg/day, has marked effects against acne conglobata acting through suppression of the sebum production (secotidary to 'atrophy' of the sebaceous gland) (Peck, 1980). It also possesses anti-keratinizing properties atid has been used successfully in genetically determitied disorders of keratinization such as Darier's disease and lamellar ichthyosis.…”

Section: Treatment With Synthetic Retinoidsmentioning

confidence: 99%

“…It also possesses anti-keratinizing properties atid has been used successfully in genetically determitied disorders of keratinization such as Darier's disease and lamellar ichthyosis. Etretinate (Tigason*) has no appreciable activity against actie but is claimed to be more potent than isotretinoin in the treatmetit of psoriasiform diseases such as pustular psoriasis and keratodermas (Orfatios, 1980;Peck, 1980). It is equally effective as isotretinoin in several genodermatoses (Peck, 1980).…”

Section: Treatment With Synthetic Retinoidsmentioning

confidence: 99%

“…Etretinate (Tigason*) has no appreciable activity against actie but is claimed to be more potent than isotretinoin in the treatmetit of psoriasiform diseases such as pustular psoriasis and keratodermas (Orfatios, 1980;Peck, 1980). It is equally effective as isotretinoin in several genodermatoses (Peck, 1980). The excellent results with etretinate therapy in a child suffering from cotigenita!…”

Section: Treatment With Synthetic Retinoidsmentioning

confidence: 99%

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Clinical use of vitamin A and its derivatives- physiological and pharmacological aspects*

Vahlquist

1985

Clin Exp Dermatol

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Section: Treatment With Synthetic Retinoidsmentioning

confidence: 99%

Section: Treatment With Synthetic Retinoidsmentioning

confidence: 99%

Section: Treatment With Synthetic Retinoidsmentioning

confidence: 99%

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Clinical use of vitamin A and its derivatives- physiological and pharmacological aspects*

Vahlquist

1985

Clin Exp Dermatol

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“…The major symptoms of synthetic retinoid acute toxicity are those of mucocutaneous drying and chapping: cheilitis, facial dermatitis, conjunctivitis (31 ), xerosis with itching, dryness of the nasal mucosa with minor nosebleeds, dry mouth with thirst, excessive palmoplantar desquamation, stratum cor- neum fragility (increased peeling with minor trauma), and hair loss (32). One case of temporary bilateral corneal opacities due to isotretinoin has been reported (33).…”

Section: Acute Toxicitymentioning

confidence: 99%

Oral Synthetic Retinoid Treatment in Children

DiGiovanna

Peck

1983

Pediatric Dermatology

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The synthetic retinoids are a new class of drugs which are highly effective in the treatment of a broad spectrum of dermatologic disease. In this report 15 patients with chronic disorders of keratinization and one patient with severe cystic acne were treated with oral isotretinoin. The degree of clinical response and duration of post-treatment remission varied with the different disorders. Acute side effects were predominantly limited to the skin and mucous membranes and were reversible after discontinuation of treatment in these patients. Acute retinoid toxicity and the potential for developing chronic toxicity are reviewed. In an attempt to facilitate the monitoring of dermatologic patients treated with oral synthetic retinoids, we present our current guidelines for the use of these agents.

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“…1 At the time, chemists were searching for alternatives to natural retinoids which, while known to be efficacious treatments for skin diseases, effects on cancer cells have largely been to act as differentiating inducers but not as cytotoxic agents, with oncology clinical activity seen in only limited settings. [2][3][4] 4-HPR generated interest in initial screening experiments because it exhibited lower toxicity and better tissue distribution than both its natural congeners and other synthetics such as retinyl acetate. 5,6 Subsequent preclinical studies have shown that 4-HPR has chemopreventative activity in several animal models, [7][8][9][10] as well as cytotoxic activity in a variety of human cancer cell lines in vitro, including head and neck, non-small cell lung cancer, small cell lung cancer, breast cancer, ovarian cancer, prostate cancer, neuroblastoma, Ewing's family of tumor, leukemia, multiple myeloma, and pancreatic cancer at concentrations of 1-10 mmol/L.…”

Section: Introductionmentioning

confidence: 99%

Clinical development of fenretinide as an antineoplastic drug: Pharmacology perspectives

Cooper

Reynolds

Cho

et al. 2017

Exp Biol Med (Maywood)

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Fenretinide (4-HPR) is a synthetic retinoid that has cytotoxic activity against cancer cells. Despite substantial in vitro cytotoxicity, response rates in early clinical trials with 4-HPR have been less than anticipated, likely due to the low bioavailability of the initial oral capsule formulation. Several clinical studies have shown that the oral capsule formulation at maximum tolerated dose (MTD) achieved <10 µmol/L concentrations in patients. To improve bioavailability of 4-HPR, new oral powder (LYM-X-SORB®, LXS) and intravenous lipid emulsion (ILE) formulations are being tested in early-phase clinical trials. ILE 4-HPR administered as five-day continuous infusion achieved over 50 µmol/L at MTD with minimal systemic toxicities; multiple complete and partial responses were observed in peripheral T cell lymphomas. The LXS oral powder 4-HPR formulation increased plasma levels approximately two-fold at MTD in children without dose-limiting toxicities and demonstrated multiple complete responses in recurrent neuroblastoma. The clinical activity observed with new 4-HPR formulations is attributed to increased bioavailability. Phase I and II clinical trials of both LXS 4-HPR and ILE 4-HPR are in progress as a single agent or in combination with other drugs. Impact statement One of the critical components in drug development is understanding pharmacology (especially pharmacokinetics) of the drugs being developed. Often the pharmacokinetic properties, such as poor solubility leading to poor bioavailability, of the drug can limit further development of the drug. The development of numerous drugs has often halted at clinical testing stages, and several of them were due to the pharmacological properties of the agents, resulting in increased drug development cost. The current review provides an example of how improved clinical activity can be achieved by changing the formulations of a drug with poor bioavailability. Thus, it emphasizes the importance of understanding pharmacologic characteristics of the drug in drug development.

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Retinoids in dermatology: an interim report

Cited by 13 publications

References 0 publications

Clinical use of vitamin A and its derivatives- physiological and pharmacological aspects*

Clinical use of vitamin A and its derivatives- physiological and pharmacological aspects*

Oral Synthetic Retinoid Treatment in Children

Clinical development of fenretinide as an antineoplastic drug: Pharmacology perspectives

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