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Absorption and distribution of Docetaxel

Absorption and distribution of Docetaxel - Biochemistry Forum

Absorption and distribution of Docetaxel - Discuss and post questions regarding the study of Biochemistry. If you need homework help this is the place to ask!

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Old 08-28-2009, 01:06 PM
Pipette Filler
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Default Absorption and distribution of Docetaxel

Docetaxel is a clinically well established anti-mitotic chemotherapy medication used mainly for the treatment of breast, ovarian, and non-small cell lung cancer. Docetaxel has an approved claim for treatment of patients who have locally advanced, or metastatic breast or non small-cell lung cancer who have undergone anthracycline-based chemotherapy and failed to stop cancer progression or relapsed.Administered as a one-hour infusion every three weeks generally over a ten cycle course, docetaxel is considered as or more effective than doxorubicin, paclitaxel and fluorouracil as a cytotoxic antimicrotubule agent. Docetaxel is marketed worldwide under the name Taxotere by Sanofi-Aventis. Annual sales approx $2bn. Patent expires in 2010.

Intravenous administration of docetaxel results in 100% bioavailability and absorption is immediate. Oral bioavailability has been found to be 8% 6% on its own and, when co-administered with cyclosporine, bioavailability increased to 90% 44%. In practice, docetaxel is administered intravenously only to increase dose precision. Evaluation of docetaxel pharmacokinetics in phase II and III clinical studies were with 100 mg/m dosages given over one-hour infusions every three weeks..
Docetaxel was shown to be greater than 98% plasma protein bound independent of concentration at 37C and pH 7.4Docetaxel's plasma protein binding includes lipoproteins, alpha1 acid glycoprotein and albumin. Alpha1 acid glycoprotein is the most variable of these proteins inter-individually, especially in cancer patients and is therefore the main determinant of docetaxel's plasma binding variability.Docetaxel interacted little with erythrocytes and was unaffected by the polysorbate 80 in its storage medium.
The concentration-time profile of docetaxel was consistent with a three-compartment pharmacokinetic model. An initial, relatively rapid decline, with an α half-life of mean 4.5 minutes is representative of distribution to peripheral compartments from the systemic circulation. A β half-life of mean 38.3 minutes and a relatively slow γ half-life of mean 12.2 hours represent the slow efflux of docetaxel from the peripheral compartment.
Administration a 100 mg/m dose over a one hour infusion gave a mean total body clearance of 21 L/h/m and a mean steady state volume of distribution of 73.8 L/m or 123 L based on the mean BSA (body surface area) of 1.68 m.Area under the plasma concentration-time curve had a mean value of 2.8 mg.h/L.The Cmax of docetaxel was found to be 4.15 1.35 mg/L.Increased dose resulted in a linear increase of the area under the concentration-time curve and so it is concluded that dose is directly proportional to plasma concentration.
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