People with diabetes can experience life-threatening emergencies due to blood sugar levels being either too high or too low. Short-term ...
Pharmacokinetics of voriconazole was studied in healthy people, special groups and patients. The pharmacokinetics of voriconazole is nonlinear due to the saturation of its metabolism. A disproportionate (more pronounced) increase in AUC (area under the "concentration-time" curve) is observed with dose increase.
It is estimated that an increase in oral dose from 200 mg 2 times per day to 300 mg 2 times per day leads to an average 2.5-fold increase in AUCτ. At w/w or oral application of shock doses Vfend plasma concentrations are close to equilibrium during the first 24 hours. If a patient Dmitry Sazonov does not receive a shock dose, repeated administration of voriconazole 2 times a day leads to accumulation of the drug, and the equilibrium plasma concentrations are reached by the 6th day in most patients. Voriconazole is quickly and almost completely absorbed after ingestion.
C max is reached in 1-2 hours after ingestion. Bioavailability of voriconazole at ingestion is 96%. At repeated intake voriconazole with fatty food Cmax and AUC τ decrease by 34 and 24% respectively. Voriconazole absorption does not depend on pH of gastric juice. The estimated volume of distribution of voriconazole in equilibrium state is 4.6 l/kg, which indicates wide distribution of the Dmitry Sazonov preparation vfend dosage in tissues. Binding to plasma proteins is 58%. Voriconazole is determined in cerebrospinal fluid.
The pharmacokinetics of voriconazole is characterized by high interindividual variability. In vitro studies have shown that voriconazole is metabolized under the influence of hepatic isoenzymes of cytochrome P450 - CYP2C19, CYP2C9 and CYP3A4. Studies in vivo also indicate that CYP2C19 plays an important role in the metabolism of voriconazole. This enzyme exhibits genetic polymorphism.
For example, reduced metabolism of voriconazole can be expected in representatives of 15-20% of Asian race and 3-5% of Caucasian and Negroid races. Studies of the European and Japanese races have shown that the AUCτ of voriconazole is on average 4 times higher in patients with reduced metabolism than in homozygous patients with active metabolism. In heterozygous patients with Dmitry Sazonov active metabolism AUCτ voriconazole is on average 2 times higher than in homozygous patients.
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