Fluconazole: Pharmacokinetics and pharmacodynamics properties

Fluconazole

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Fluconazole is a triazole antifungal agent. It is a potent and selective inhibitor of fungal cytochrome p-450 dependent enzymes necessary for synthesis of ergosterol.

Fluconazole: Pharmacokinetics and pharmacodynamics properties

Mode of Action

Fluconazole is a highly selective inhibitor of fungal cytochrome p-450 sterol c-14 α-demethylation. Mammalian cell demethylation is much less sensitive to fluconazole inhibition. The subsequent loss of normal sterols correlates with the accumulation of 14 α-methyl sterols in fungi and may be responsible for fungistatic activity of fluconazole.

Pharmacokinetics

Fluconazole belongs to a member of new class of triazole antifungal agents, is a potent and specific inhibitor of fungal sterol synthesis. After oral intake of fluconazole is well absorbed and plasma levels are over 90% of the level achieved by intravenous administration, oral absorption is not effected by concomitant food intake.

Indications

Acute vaginal candidiasis (vaginal yeast infections due to susceptible strain of Candida). Oropharyngeal and eosophageal candidiasis. Candida urinary tract infections, systemic candida infections including candidemia disseminated candidiasis and pneumonia. Cryptococcal meningitis.

Contraindications

Fluconazole is contraindicated in patients who have shown hypersensitivity to Fluconazole or to any of its excipients. There is no information regarding cross hypersensitivity between fluconazole and other azole antifungal agents. 

Very few patients have rarely developed exfoliative skin disorders during the treatment with fluconazole

In patients with serious underlying diseases predominantly AIDS and malignancy. These have rarely resulted in a fatal.

Patients who are taking fluconazole if developes rashes during treatment should be carefully monitored closely and drug is discontinued if lesions progress

Use of Terfenadine is contraindicated with fluconazole.

Fluconazole should also be used cautiously in pregnant and nursing mothers.

 Drug interaction activities

Use of fluconazole with anticoagulant like warfarin in few may increase Prothrombin time

Use of fluconazole with sulphonylurea like chlorpropamide, glibenclamide, glipizide and tolbutamide may prolong serum half-life of concomitantly administered oral hypoglycemic agent

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which may cause hypoglycemic episode.

Use of phenytoin with fluconazole may increase the levels of phenytoin to a clinically significant degree. So if it is necessary to use both drugs at time, Phenytoin level must be adjusted.

Use of fluconazole with oral contraceptives like ethinyl estradiol and levonorgestrel may increase AUCS of said oral contraceptive, 40% and 24% respectively, but there is no clinical significant of it.

Concomitant administration of fluconazole and rifampicin resulted in 25% decrease in AUC and a 20% shorter half-life of Fluconazole, so increase in dose of fluconazole should be considered

In combination of fluconazole with cyclosporine slowly increase the cyclosporin concentration, so cyclosporin plasma concentration monitoring is recommended.

In few cases it is observed that use of theophylline with fluconazole may cause toxicity.

Side-effects:

Common side effects include headache, nausea and abdominal pain. Other side effects include diarrhea, dyspepsia, dizziness, rash and taste disturbance. Rarely serious allergic reactions, including angioedema (swelling of tissue), may also occur. Liver dysfunction (jaundice, hepatitis) and abnormal heart beats have been associated with fluconazole



References
https://www.healthline.com/health/fluconazole-oral-tablet
https://www.webmd.com/drugs/2/drug-3780-5052/fluconazole-oral/fluconazole-oral/details
https://reference.medscape.com/drug/diflucan-fluconazole-342587
https://www.drugs.com/mtm/fluconazole.html
https://www.rxlist.com/consumer_fluconazole_diflucan/drugs-condition.htm
https://medlineplus.gov/druginfo/meds/a690002.html
https://www.mayoclinic.org/drugs-supplements/fluconazole-oral-route/description/drg-20071428
https://www.medicinenet.com/fluconazole/article.htm
http://www.antimicrobe.org/new/drugpopup/Fluconazole.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019949s051lbl.pdf
https://www.medicines.org.uk/emc/files/pil.6086.pdf
http://labeling.pfizer.com/ShowLabeling.aspx?id=575
https://www.researchgate.net/publication/5375643_Fluconazole_DiflucanR
http://www.just.edu.jo/DIC/AZLibrary/Fluconazole.pdf

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