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. Metabolism and excretion
Docetaxel is mainly metabolised in the liver by the cytochrome P450 CYP3A4 and CYP3A5 subfamilies of isoenzymes. Metabolism is principally oxidative and at the tert-butylpropionate side chain, resulting first in an alcohol docetaxel (M2), which is then cyclised to three further metabolites (M1, M3 and M4). M1 and M3 are two diastereomeric hydroxyoxazolidinones and M4 is an oxazolidinedione. Phase II trials of 577 patients showed docetaxel clearance is related to body surface area and to hepatic enzyme and alpha1 acid glycoprotein plasma levels. The following model represents docetaxel clearance in humans:

where CL is total body clearance (L/h), BSA is total body surface area (m2), AAG and ALB represent alpha1 acid glycoprotein and albumin plasma concentrations (g/L) respectively, and AGE is the patients age (years). HEP12 represents a measure of hepatic dysfunction, affecting clearance of docetaxel. This final model accounted for a modest proportion of patients and identified most of the patients varying from the model (population median of CL = 35.6 L/h) as having hepatic dysfunction, indicating hepatic function as the most unpredictable factor with regards to clearance variability.Patients with significant hepatic dysfunction had an approximately 30% decrease in clearance of docetaxel and were also at a higher risk of toxicity poisoning from docetaxel treatment.
Gustatory hyperhidrosis is excessive sweating classified under focal hyperhidrosis, that is, it is restricted to certain regions of the body. Affected people regularly experience this on the forehead (scalp), upper lip, perioral region, or sternum a few moments after eating spicy foods, tomato sauce, chocolate, coffee, tea, or hot soups.A common cause is trauma or damage to the nerve that passes through the parotid gland, which can be due to surgery of the parotid gland (parotidectomy). This type of sweating is known as Freys syndrome. Gustatory hyperhidrosis has been observed in diabetics with autonomic neuropathy, and a variant of this disorder has been reported following surgical sympathectomy.Around 10% of affected people require treatment. One of the more effective treatments is oral or topically applied glycopyrrolate. == References ==