Isotretinoin

Isotretinoin is a medication used for the treatment of severe acne. It is sometimes used as a chemotherapy medication for prevention and treatment of certain skin cancers. In some cases, it is used to treat Harlequin type ichthyosis, a usually lethal skin deformation in which sufferers develop armor plated-like skin and usually die soon after birth. It is a retinoid, meaning it derives from vitamin A and is found in smallquantities naturally in the body. Oral isotretinoin is marketed under various trade names, most commonly Accutane (Roche), Amnesteem (Mylan),Claravis (Barr), Decutan (Actavis), Isotane (PacificPharmaceuticals), Sotret (Ranbaxy), Oratane(GenepharmAustralasia) or Roaccutane (Roche), Izotek (BlauFarma);while topical isotretinoin is most commonly marketed under the trade names Isotrex or Isotrexin (Stiefel).

Isotretinoin

General Information :

• CAS number : 4759-48-2
• ATC code : D10AD04
• PubChem : 5282379
• DrugBank : APRD00140
• ChemSpider : 4445539
• Formula : C20H28O2
• Mol. Mass : 300.44 g/mol
• Bioavability : Variable
• Protein binding : 99.9%
• Metabolism : Hepatic
• Half life : 10 – 20 hours
• Excretion : Renal and Fecal
• Licence data : US
• Routes : Oral, Topical

Isotretinoin's exact mechanism of action is unknown. However it is known that, like other retinoid, the drug alters DNA transcription. This effect decreases the size and output of sebaceous glands, making the cells that are sloughed off into the sebaceous glands less sticky, and therefore less ableto form comedones. Isotretinoin noticeably reduces the production of sebum and shrinks the sebaceous glands. It stabilizes keratization and prevents come dones from forming. This combined impact on several of the contributory factors inacne distinguishes isotretinoin from alternative remedies such as antibiotics and accounts for its greater efficacy in severe, nodulocystic cases.

Isotretinoin, when administered orally, is best absorbed when taken after a high fat meal, as it has a high level of lipophilicity. In across over study, it was found that the peak plasma concentration more than doubled when taken after a high fat meal versus a fasted condition.Isotretinoin is primarily (99.9%) bound to plasma proteins, mostly albumin. At least three metabolites have been detected in human plasma after oral administration of isotretinoin. These are 4-oxo-isotretinoin, retinoic acid and4-oxo-retinoic acid. Isotretinoin also oxidises, irreversibly, to4-oxo-isotretinoin. The metabolites of isotretinoin are excreted through bothurine and feces. The mean elimination half-life is 21 hours, with a standard deviation from this mean of 8.2 hours.

Currently, isotretinoin continues to be used only after other acne treatments fail to produce results. Treatment of acne begins with topical medications (e.g. benzoyl peroxide, adapalene , etc), followed by oralantibiotics (or a combination) and finally isotretinoin therapy. This isbecause other treatments, while less effective than isotretinoin, are thoughtto be associated with fewer adverse effects and lower cost. The higher cost is due to the medical supervision required in taking a toxic dosage. The cost ofthe medicine is also a factor (example: taking 5, 10, or even 20mg daily is farless expensive than taking 80mg daily).

The dose of isotretinoin a patient receives is dependent on their weight and the severity of the condition. High dose treatments are administered between 0.5 mg/kg/day to 2 mg/kg/day (usually at 0.5 to 1mg/kg/day, divided into two doses), for a total treatment of 4–6 months. Asecond course may be used two months following the cessation of the initial course if severe acne recurs. Efficacy appears to be related to the cumulative dose of isotretinoin taken, with a total cumulative dose of 120–150 mg/kg usedas a guideline. High dose treatments should only be used as a last resort due to adverse side effects.

Other studies show that lower dosage treatments are just aseffective. In these experiments, subjects used 20mg/day, which is 0.25mg/kg/day for an 80 kg (176 pounds) person.

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