Contrasting effects of fluconazole and ketoconazole on phenytoin and testosterone disposition in man.

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Touchette MA, Chandrasekar PH, Milad MA, Edwards DJ

Contrasting effects of fluconazole and ketoconazole on phenytoin and testosterone disposition in man.

Br J Clin Pharmacol. 1992 Jul;34(1):75-8.

PubMed ID

1633070 [ View in PubMed

]

Abstract

Nine healthy male subjects received oral fluconazole 400 mg daily, ketoconazole 200 mg twice daily or no treatment for 6 days according to a randomized, cross-over design. A single 250 mg oral dose of phenytoin suspension was administered on day 5 and serum phenytoin concentrations were measured over the following 48 h. Serum testosterone concentrations were measured for 10 h after each dose of phenytoin. Ketoconazole had no significant effect on phenytoin concentrations while the mean AUC(0,48) for phenytoin was significantly higher with fluconazole (195.2 +/- 47.8 micrograms ml-1 h) than control (146.3 +/- 49.6 micrograms ml-1 h). At 48 h, the serum phenytoin concentration averaged 1.72 micrograms ml-1 under control conditions and 3.99 micrograms ml-1 with fluconazole (132% increase). AUC(0,10) for testosterone was 42% lower than control after ketoconazole administration (P less than 0.05) but increased by 33% from 55.6 +/- 9.4 ng ml-1 h (control) to 73.8 +/- 12.6 ng ml-1 h with fluconazole. AUC(0,10) values for the testosterone precursors androstenedione and 17 alpha-hydroxyprogesterone were significantly higher in the fluconazole treatment phase as were concentrations of luteinizing hormone. The mechanism and clinical significance of the increase in testosterone concentration caused by fluconazole remains to be determined.

DrugBank Data that Cites this Article

Drug Interactions

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drugs	Interaction
Integrate drug-drug interactions in your software
Fosphenytoin Ketoconazole	The serum concentration of Fosphenytoin can be increased when it is combined with Ketoconazole.
Phenytoin Ketoconazole	The serum concentration of Phenytoin can be increased when it is combined with Ketoconazole.

Pharmaco-metabolomics

Drug	Drug Groups	Metabolite	Change	Description
Fluconazole	Approved Investigational	Testosterone	increased	Fluconazole increases the level of Testosterone in the blood
Ketoconazole	Approved Investigational	Testosterone	decreased	Ketoconazole decreases the level of Testosterone in the blood