Treatment voriconazole determination of serum levels in the affecting factors in patients voriconazole

Voriconazole is a broad-spectrum triazole antifungal used for the treatment of invasive fungal infections. Voriconazole is metabolized primarily by the P450 enzyme CYP2C19, CYP2C9 and CYP3A4. Some factors that affect these enzymes like genetic background, age, liver functions and co-administration of some drugs, effect metabolism and plasma level of voriconazole. Variety of pharmacokinetics of voriconazole can be related to decrease of its efficacy and toxicity. Hence measurement of voriconazole plasma levels will be important for its efficacy and toxicity. We purposed that measurement of voriconazole in serum and determine the factors that effect safety and plasma pharmacokinetics in patients with fungal infection receiving voriconazole therapy. Plasma voriconazole concentrations were analyzed for plasma samples drawn at 24th h, 48th h and 7th day. We identified 29 patients who underwent 77 voriconazole plasma concentrations measurements. We determined the level of serum voriconazole using high-performance liquid Chromatography (HPLC) modified from the method as described by Roffey et al. The serum concentrations did not related with age, sex and co-administrated drugs. Hence there is no need to adjust the dosage according to these parameters. The administration route does not affect the serum level. In our study, daily amount dose of voriconazole did not affect the effective concentration 1 ?g/ml and above. We did not determine a significant correlation between the serum concentrations and the efficacy and mortality. In our study, we compared steady-state concentrations in patients given loading dose with not given. Steady-state concentrations were achieved within 24 h if a loading dose is given on day 1. Hence loading dose should be given. In patients who have hipoproteinemia at the beginning of the therapy serum level of voriconazole was higher significantly. Low serum protein levels are an important factor to reach toxic levels. Above 400 mg/day doses are important factors for reaching to plasma trough levels greater than 5.5 mg/L which is toxic level. Factors affecting mortality are daily drug doses higher than 400 mg, high serum GGT levels at the beginning of the therapy and low serum protein levels.