With the aromatic retinoic acid analog Tigason oral and intravenous pharmacokinetic studies have been performed in 5 normal volunteers. Simultaneous fitting of single i. v. and oral data to a three-compartment model assuming first-order absorption was possible. Using Nonlin parameter estimates of the single-dose data, one is able to predict the decline in plasma levels of parent drug following cessation of a 10 days multiple dosing regimen up to 24 hours. The model is however unable to predict a phase of prolonged elimination observed beyond 24 hours. Moreover in 5 patients, who underwent…mehr
With the aromatic retinoic acid analog Tigason oral and intravenous pharmacokinetic studies have been performed in 5 normal volunteers. Simultaneous fitting of single i. v. and oral data to a three-compartment model assuming first-order absorption was possible. Using Nonlin parameter estimates of the single-dose data, one is able to predict the decline in plasma levels of parent drug following cessation of a 10 days multiple dosing regimen up to 24 hours. The model is however unable to predict a phase of prolonged elimination observed beyond 24 hours. Moreover in 5 patients, who underwent chronic therapy (8-15 months), substantial plasma levels of both unchanged drug and main metabolite (corre sponding carboxylic acid) were observed up to 140 days after cessation of the therapy. An apparent half-life of elimination of 80-100 days can be calculated. The drug appears to be stored at some yet unknown storage site. Investigation of metabolism of Tigason in rats and humans revealed 19different bio transformation products thus far, most of them appearing in the urine in low amounts (20010 of dose). A few of them (mainly the acid Ro 10-1670) after conjugation to glucuronic acid are excreted in the bile in high amounts (60-80% of dose). No drug appeared unchanged in the excreta after i. v. administration to rats. References 1. Bollag W (1971) Effects of vitamin A acid (NSC-122758) on transplantable and chemically-induced tumors. Cancer Chemother Rep 55:53-58 2.
Pharmacology and Toxicology of Retinoids.- From Vitamin A to Retinoids: Chemical and Pharmacological Aspects.- Pharmacokinetics and Metabolism of Oral Aromatic Retinoids.- In vivo Immunostimulating Properties of Two Retinoids: Ro 10-9359 and Ro 13-6298.- Vitamin A Transport and Delivery and the Mechanism of Vitamin A Toxicity.- Experimental Toxicology of the Aromatic Retinoid Ro 10-9359 (Etretinate).- Studies in Reproductive Toxicology and Mutagenicity with Ro 10-9359.- Cytogenetic Studies in Patients Treated with Oral Retinoid Ro 10-9359.- Chromosomal Analysis in Patients Treated with the Oral Aromatic Retinoid Ro 10-9359.- Biological Effects of Retinoids.- Retinoids: New Developments in Their Mechanism of Action as Related to Control of Proliferative Diseases.- The Effects of Retinoids on Stratum Corneum. Structure and Function.- Light- and Electron Microscopic Changes of Human Epidermis Under Oral Retinoid Treatment.- Retinoid-Stimulated Material in Psoriatic Epidermis During Ro 10-9359 Therapy.- Effects of Oral Retinoid on Dermal Components in Human and Animal Skin.- Retinoid-binding Proteins and the Plasma Transport of Etretinate (Ro 10-9359) in Man.- Biochemical Mechanism of Modulation of Skin Carcinogenesis by Retinoids.- Mitogenic Properties of Aromatic Retinoids: in vivo and in vitro Effects on Epidermal Cells.- On the Effects Induced by Aromatic Retinoid Ro 10-9359 on Explants of Skin from Psoriatic Patients.- Effects of Retinoids on Keratinocytes in vitro.- Influence of Retinoid on Human Blood Cells in vitro. TMMP-retinoid Inhibits the Mitogenic Properties of Lectins and Modulates the Lymphocytic Response.- Ro 10-9359 Retinoid Inhibits Both in vitro Epidermal Cell Proliferation and Differentiation.- Application of Oral Retinoids in Psoriasis.- Aromatic Retinoids in Psoriasis: Clinical, Histological, Histochemical, Electron Microscopical and Immunological Investigations.- Intermittent Dose Schedule of Retinoids (Ro 10-9359) for Long-term Follow-up on Psoriasis (Preliminary Report).- Treatment of Severe Forms of Psoriasis with a Retinoic Acid Derivative: Ro 10-9359.- Treatment of Psoriasis Vulgaris with a Low-dosage Ro 10-9359 (Tigason) Orally Combined with Corticosteroids Topically.- Aromatic Retinoid (Ro 10-9359), RePUVA and PUVA in the Treatment of Psoriasis.- Clinical Observations on Oral Retinoid Therapy of Psoriatic Arthropathy (Ro 10-9359).- Application of Oral Retinoids in Acne.- Effects of Retinoids on the Sebaceous Glands of the Hamster Flank Organ.- Effects of Two Retinoids in Animal Experiments and After Clinical Application in Acne Patients: 13-cis Retinoic Acid Ro 4-3780 and Aromatic Retinoid Ro 10-9359.- Oral Retinoids: Effects on Human Sebaceous Glands and Nodulocystic Acne.- Oral Vitamin A (Retinol) in Acne Vulgaris.- 13-cis Retinoic Acid in Acne (A Double-blind Study of Dose Response).- Effects of 13-cis Retinoic Acid on Sebaceous Glands in Humans.- A Clinical Trial of the Use of Tigason (Ro 10-9359) in Male Patients with Severe Acne Vulgaris.- Oral Retinoid Therapy of Miscellaneous Disorders of Skin and Oral Mucosa.- Treatment of Lichen Planus and Leukoplakia with the Oral Retinoid Ro 10-9359.- Comparative Analysis of Two Retinoids in the Treatment of Disorders of Keratinization.- Long-Term Follow-up of 30 Children Under Oral Retinoid Ro 10-9359..- Treatment of Erythrokeratodermia Variabilis with Oral Retinoid (Ro 10-9359).- Ultrastructural Study of the Four Main Types of Ichthyosis After one Month's Treatment with Ro 10-9359.- Effect of Retinoids on Precancerous Lesions of Oral Mucosa.- Treatment of Parapsoriasis en Plaques and Mycosis Fungoides with an Oral Aromatic Retinoid (Ro 10-9359).- Effects of Retinoid Ro 10-9359 Alone or in Combined Therapy in Several Skin Diseases - Clinical Observations and Biochemical Data.- Effect of Systemic Ro 10-9359 Treatment of Immunological Parameters in Darier's Disease.- Freeze-Fracture Study of Psoriatic Lesions After Oral Administration of Retinoid.- Psor
Pharmacology and Toxicology of Retinoids.- From Vitamin A to Retinoids: Chemical and Pharmacological Aspects.- Pharmacokinetics and Metabolism of Oral Aromatic Retinoids.- In vivo Immunostimulating Properties of Two Retinoids: Ro 10-9359 and Ro 13-6298.- Vitamin A Transport and Delivery and the Mechanism of Vitamin A Toxicity.- Experimental Toxicology of the Aromatic Retinoid Ro 10-9359 (Etretinate).- Studies in Reproductive Toxicology and Mutagenicity with Ro 10-9359.- Cytogenetic Studies in Patients Treated with Oral Retinoid Ro 10-9359.- Chromosomal Analysis in Patients Treated with the Oral Aromatic Retinoid Ro 10-9359.- Biological Effects of Retinoids.- Retinoids: New Developments in Their Mechanism of Action as Related to Control of Proliferative Diseases.- The Effects of Retinoids on Stratum Corneum. Structure and Function.- Light- and Electron Microscopic Changes of Human Epidermis Under Oral Retinoid Treatment.- Retinoid-Stimulated Material in Psoriatic Epidermis During Ro 10-9359 Therapy.- Effects of Oral Retinoid on Dermal Components in Human and Animal Skin.- Retinoid-binding Proteins and the Plasma Transport of Etretinate (Ro 10-9359) in Man.- Biochemical Mechanism of Modulation of Skin Carcinogenesis by Retinoids.- Mitogenic Properties of Aromatic Retinoids: in vivo and in vitro Effects on Epidermal Cells.- On the Effects Induced by Aromatic Retinoid Ro 10-9359 on Explants of Skin from Psoriatic Patients.- Effects of Retinoids on Keratinocytes in vitro.- Influence of Retinoid on Human Blood Cells in vitro. TMMP-retinoid Inhibits the Mitogenic Properties of Lectins and Modulates the Lymphocytic Response.- Ro 10-9359 Retinoid Inhibits Both in vitro Epidermal Cell Proliferation and Differentiation.- Application of Oral Retinoids in Psoriasis.- Aromatic Retinoids in Psoriasis: Clinical, Histological, Histochemical, Electron Microscopical and Immunological Investigations.- Intermittent Dose Schedule of Retinoids (Ro 10-9359) for Long-term Follow-up on Psoriasis (Preliminary Report).- Treatment of Severe Forms of Psoriasis with a Retinoic Acid Derivative: Ro 10-9359.- Treatment of Psoriasis Vulgaris with a Low-dosage Ro 10-9359 (Tigason) Orally Combined with Corticosteroids Topically.- Aromatic Retinoid (Ro 10-9359), RePUVA and PUVA in the Treatment of Psoriasis.- Clinical Observations on Oral Retinoid Therapy of Psoriatic Arthropathy (Ro 10-9359).- Application of Oral Retinoids in Acne.- Effects of Retinoids on the Sebaceous Glands of the Hamster Flank Organ.- Effects of Two Retinoids in Animal Experiments and After Clinical Application in Acne Patients: 13-cis Retinoic Acid Ro 4-3780 and Aromatic Retinoid Ro 10-9359.- Oral Retinoids: Effects on Human Sebaceous Glands and Nodulocystic Acne.- Oral Vitamin A (Retinol) in Acne Vulgaris.- 13-cis Retinoic Acid in Acne (A Double-blind Study of Dose Response).- Effects of 13-cis Retinoic Acid on Sebaceous Glands in Humans.- A Clinical Trial of the Use of Tigason (Ro 10-9359) in Male Patients with Severe Acne Vulgaris.- Oral Retinoid Therapy of Miscellaneous Disorders of Skin and Oral Mucosa.- Treatment of Lichen Planus and Leukoplakia with the Oral Retinoid Ro 10-9359.- Comparative Analysis of Two Retinoids in the Treatment of Disorders of Keratinization.- Long-Term Follow-up of 30 Children Under Oral Retinoid Ro 10-9359..- Treatment of Erythrokeratodermia Variabilis with Oral Retinoid (Ro 10-9359).- Ultrastructural Study of the Four Main Types of Ichthyosis After one Month's Treatment with Ro 10-9359.- Effect of Retinoids on Precancerous Lesions of Oral Mucosa.- Treatment of Parapsoriasis en Plaques and Mycosis Fungoides with an Oral Aromatic Retinoid (Ro 10-9359).- Effects of Retinoid Ro 10-9359 Alone or in Combined Therapy in Several Skin Diseases - Clinical Observations and Biochemical Data.- Effect of Systemic Ro 10-9359 Treatment of Immunological Parameters in Darier's Disease.- Freeze-Fracture Study of Psoriatic Lesions After Oral Administration of Retinoid.- Psor
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