Experimental Toxicology of the Aromatic Retinoid Ro 10-9359 (Etretinate)

Teelmann, Kampe

doi:10.1007/978-3-642-68023-6_6

Cited by 18 publications

(6 citation statements)

References 8 publications

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“…After long-term admininstration of high doses of isotretinoin (2-4 mg/kg body weight), a retinoid related to etretinate, adverse effects, such as premature closure of the growth plate [16] and an ossification disorder resembling idiopathic cortical hyperostosis [5,21], have been reported. Accelerated ossification and increased porosity of the bones were observed in rats given 3 mg etretinate/kg body weight [28]. With therapeutic doses of etretinate (0.5-1.5 mg/kg body weight), however, there has so far been no evidence of any bone changes or growth inhibition.…”

Section: Toxicologymentioning

confidence: 96%

Etretinate therapy in children with severe keratinization defects

Traupe

Happle

1985

Eur J Pediatr

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Keratinization defects can be very severe and disfiguring diseases. The development of retinoids such as etretinate has provided us with an effective symptomatic form of oral therapy for these skin conditions. Based on our own experience, we briefly outline the therapeutic potential of etretinate in various keratinization defects (lamellar ichthyosis, Netherton syndrome, Sjögren-Larsson syndrome, mal de Meleda and juvenile pityriasis rubra pilaris). The toxicology of etretinate is reviewed with special regard to the treatment of children. Bone changes such as premature closure of the growth line or other unacceptable side-effects have so far not been observed. Guidelines for patient selection and for the safe treatment of children are given.

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Section: Toxicologymentioning

confidence: 96%

Etretinate therapy in children with severe keratinization defects

Traupe

Happle

1985

Eur J Pediatr

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“…There are several indications that the synthetic retinoids may be capable of inducing similar chronic bone toxicities. Teelmann (58) recently reported accelerated ossification of the epiphyseal line in rats given 3 mg/kg/day of etretinate. Premature closure of the epiphyses is one vitamin A toxicity that would be of great concern in the treatment of children.…”

Section: Chronic Bone and Joint 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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“…In some respects, these general signs of BMS-189453 toxicity are similar to those produced by excessive vitamin A intake or administration of retinoid agonists. For example, erythema is a common clinical sign of toxicity in rodents, following oral administration of vitamin A at 3 to 6 mg/kg, 13-cis-retinoic acid at 15 to 20 mg/kg, all trans-retinoic acid at 5 to 50 mg/kg, or etretinate at 10 to 15 mg/kg (Kamm, 1982;Teelmann, 1981). Oral administration of the retinoid agonists SMR2 or SMR6 to mice at doses from 0.1 to 0.4 mg/kg resulted in a 2-to 4-fold elevation in leukocyte counts (Lindamood et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

BMS-189453, a Novel Retinoid Receptor Antagonist, Is a Potent Testicular Toxin

Schulze

Clay

Mezza

et al. 2001

Toxicological Sciences

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BMS-189453 is a synthetic retinoid that acts as an antagonist at retinoic acid receptors alpha, beta, and gamma. In Sprague Dawley rats at daily oral doses of 15, 60, or 240 mg/kg for 1 month, BMS-189453 produced increases in leukocyte counts, alkaline phosphatase and alanine aminotransferase levels, and marked testicular degeneration and atrophy at all doses. Significant overt signs of toxicity and deaths occurred at 240 mg/kg, whereas body-weight and food-consumption decreases occurred at 60 and 240 mg/kg. When BMS-189453 was administered to male rats at daily doses ranging from 12.5 to 100 mg/kg for 1 week, only minimal testicular changes occurred at all doses, shortly after the dosing period. However, after a 1-month drug-free observation period, marked testicular atrophy was evident at all doses. BMS-189453 was then administered at doses of 2, 10, or 50 mg/kg to male rats for 1, 3, or 7 consecutive days. Dose- and duration-dependent testicular toxicity that occurred after a 1-month observation period did not recover, and, in some cases, was more severe 4 months after the last dose. In rabbits administered BMS-189453 at oral doses of 2, 10, or 50 mg/kg for 1 week, testicular degeneration and atrophy were evident in the high-dose group at 1 month following treatment. These studies indicate that retinoid antagonists can selectively produce progressive and prolonged testicular toxicity after single or repeated oral doses that are otherwise well tolerated.

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Experimental Toxicology of the Aromatic Retinoid Ro 10-9359 (Etretinate)

Cited by 18 publications

References 8 publications

Etretinate therapy in children with severe keratinization defects

Etretinate therapy in children with severe keratinization defects

Oral Synthetic Retinoid Treatment in Children

BMS-189453, a Novel Retinoid Receptor Antagonist, Is a Potent Testicular Toxin

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