Docetaxel

Docetaxel 화학적 특성, 용도, 생산

• 용도

  Docetaxal is an impurity of Docetaxel (D494420), a semisynthetic derivative of Paclitaxel (P132500). Docetaxel is an antimitotic agent that promotes the assembly of micro-tubules and inhibits their de -polymerization to free tubulin.

• 일반 설명

  Docetaxel is available in single-dose vials of 20 mg/0.5 mLand 80 mg/2 mL for IV administration in the treatment of breast, NSCLC, and prostate cancers. It has also been utilizedin non–FDA-approved treatment of head, neck, gastric,bladder, and refractory ovarian cancers.
  Docetaxel is highly plasma protein bound (80%) andwidely distributed with the highest concentration in the hepatobiliarysystem, but it does not appear to cross the bloodbrainbarrier. The metabolism of docetaxel has been lesswell studied than that of paclitaxel. The use of human livermicrosomes has indicated that metabolism involves oxidationof one of the tert-butyl methyl groups of the C-13 sidechain to initially give the alcohol. Further oxidation to thealdehyde and carboxylic acid both of which may cyclizewith the carbamate nitrogen to give stereoisomeric hydroxyoxazolidinonesand an oxazolidinedione, respectively. Noactive metabolites have been identified. The major enzymeinvolved is CYP3A4. The drug is primarily eliminated in thefeces with a terminal half-life of 11 hours.
  The adverse effects profile for docetaxel is similar to thatof paclitaxel but also includes reversible fluid retention that isdose related. This has been associated with an initial increasein capillary permeability followed by a decrease in lymphaticdrainage later in the therapy. Restriction of sodium intake andpretreatment with corticosteroids is usually successful inminimizing this adverse effect. Peripheral neuropathy is seenwith docetaxel but occurs less often than with paclitaxel.Fatigue and muscle pain are commonly seen, and fever mayoccur in up to 30% of patients who are infection free.

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