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Voriconazole is a drug for the treatment of fungal infections and is a broad-spectrum antifungal agent with therapeutic effects on fungal infections in both humans and animals, and is on the World Health Organisation's list of essential medicines, which are the most effective and safest medicines required by the health system.
Voriconazole is a broad-spectrum triazole antifungal agent with the following indications: treatment of invasive aspergillosis; treatment of severe invasive infections caused by fluconazole-resistant Candida (including Candida krohnii); treatment of severe infections caused by Actinobacterium spp. and Fusarium spp. of the foot; and Voriconazole should be used primarily for the treatment of progressive, potentially life-threatening infections in immunodeficient patients.
Uses and functions of Voriconazole.
Voriconazole is a broad-spectrum triazole antifungal drug, which can inhibit the activity of lanosterol 14α-demethylase and 24-methylenedihydrolanosterol demethylase in fungal cells, thus inhibiting the synthesis of ergosterol, an important substance on the cell membrane of fungal cells, resulting in the defect of fungal cell membrane and the leakage of important cell components and death.
Voriconazole has bactericidal effect on Candida and Aspergillus fungi, and also on other pathogenic fungi.
Pharmacological Effects of Voriconazole.
Co-administration with CYP3A4 substrates, terfenadine, sirolimus, astemizole, cisapride, pimozide or quinidine increases the blood concentrations of the above drugs, resulting in prolongation of the Q-T interval and occasional tip-twisting ventricular tachycardia.
Combination with rifampicin, rifabutin, efavirenz, ritonavir (400 mg every 12 hours), carbamazepine and phenobarbital significantly reduces voriconazole blood concentrations.
Increased blood concentrations of ergot alkaloids (ergotamine, dihydroergotamine) in combination with ergot alkaloids can lead to ergotism.
The mechanism of action of voriconazole is the inhibition of cytochrome P450-mediated demethylation of 14α-sterols in fungi, thereby inhibiting ergosterol biosynthesis.
In vitro tests have shown that voriconazole has a broad-spectrum antifungal effect.
Voriconazole is antimicrobial against Candida spp. (including fluconazole-resistant Candida krusei, Candida glabrata, and Candida albicans-resistant strains), and bactericidal against all Trichoderma spp. fungi tested.
In addition, voriconazole has been shown to be bactericidal in vitro against other pathogenic fungi, including genera with low susceptibility to existing antifungal agents, such as Actinobacillus spp. and Fusarium spp.
In animal studies, the lowest inhibitory concentration of voriconazole was found to correlate with its efficacy.
However, in clinical studies, there was no correlation between the minimum inhibitory concentration and clinical efficacy, and there appeared to be no correlation between blood concentrations of the drug and clinical efficacy. This is a characteristic of pyrrole antifungals.
Production method of Voriconazole Raw Powder.
For oral administration, a loading dose should be given on the first day of initial administration so that its blood concentration approaches steady-state concentration on the first day of administration. Because of the high bioavailability of oral tablets (96%), the intravenous and oral routes of administration may be interchanged when clinically indicated.
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