Ketoconazole and Fluconazole Drug Interactions

Baciewicz, Anne M.

doi:10.1001/archinte.1993.00410170042004

Cited by 31 publications

(6 citation statements)

References 48 publications

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“…ketoconazole > itraconazole > fluconazole, with miconazole being essentially without effect (240,241). Certain macrolide antibiotics, such as erythromycin and troleandomycin, are also fairly potent inhibitors, although less than ketoconazole, as a result of their inactivation of CYP3A by the formation of complexes with the heme moiety (104,(241)(242)(243).…”

Section: Clinically Important Drug Interactionsmentioning

confidence: 99%

In Vitro and in Vivo Drug Interactions Involving Human Cyp3a

Thummel

Wilkinson

1998

Annu. Rev. Pharmacol. Toxicol.

762

515

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Cytochrome P4503A (CYP3A) is importantly involved in the metabolism of many chemically diverse drugs administered to humans. Moreover, its localization in high amounts both in the small intestinal epithelium and liver makes it a major contributor to presystemic elimination following oral drug administration. Drug interactions involving enzyme inhibition or induction are common following the coadministration of two or more CYP3A substrates. Studies using in vitro preparations are useful in identifying such potential interactions and possibly permitting extrapolation of in vitro findings to the likely in vivo situation. Even if accurate quantitative predictions cannot be made, several classes of drugs can be expected to result in a drug interaction based on clinical experience. In many instances, the extent of such drug interactions is sufficiently pronounced to contraindicate the therapeutic use of the involved drugs.

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Section: Clinically Important Drug Interactionsmentioning

confidence: 99%

In Vitro and in Vivo Drug Interactions Involving Human Cyp3a

Thummel

Wilkinson

1998

Annu. Rev. Pharmacol. Toxicol.

762

515

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“…In such patients, acid supplementation (cola drink) or drug substitution (fluconazole instead of ketoconazole 4,47 ) may be required. Interactions with other drugs, including acid suppressants such as proton pump inhibitors, 48 are more likely than age‐related changes in gastrointestinal function to lower plasma concentrations of ketoconazole below therapeutic levels. In other instances of inadequate drug response, poor compliance has to be considered as the most likely cause 49–51 …”

Section: Discussionmentioning

confidence: 99%

Gastric Function in the Elderly: Effects on Absorption of Ketoconazole

Hurwitz

Ruhl²,

Kimler³

et al. 2003

The Journal of Clinical Pharma

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The authors studied effects of age-related changes in gastric function on absorption of ketoconazole. Eighteen men and women age 65 years or older swallowed 200 mg ketoconazole on two occasions, once as tablets with water and once as tablets crushed in acidic juice. The sequence was randomly determined. Gastric pH was measured by radiotelemetry and gastric emptying rate by radiolabeled technetium with a gamma camera. Plasma ketoconazole was assayed by high-performance liquid chromatography (HPLC). Subjects with gastric pH less than or equal to 4.5 absorbed ketoconazole equally well from intact tablets and tablets crushed in acid. When pH was 5.0 or higher, ketoconazole was absorbed well from acid-crushed tablets but not from intact tablets. Gastric emptying was shown to be rapid in all subjects. Since the prevalence of such hypoacivity is approximately 5% in the elderly, and other parameters of gastric function are usually normal, impaired absorption of drugs such as ketoconazole should be uncommon with normal aging.

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“…Fluconazole also appears to inhibit the metabolism of compounds which are substrates for CYP3A, such as cyclosporine (11,23,26) and terfenadine (21). However, the extent of inhibition by fluconazole appears to be dose dependent for CYP3A substrates, as shown by animal studies with cyclosporine (24) and clinical reports of minimal or no apparent pharmacokinetic interaction between fluconazole and terfenadine (20) or cyclosporine (1,18,27). A significant interaction with terfenadine was observed only when fluconazole was given at a high dose (800 mg/day) in subjects who were poor metabolizers of terfenadine (8).…”

Section: Discussionmentioning

confidence: 99%

Effect of fluconazole on the steady-state pharmacokinetics of delavirdine in human immunodeficiency virus-positive patients

Borin¹,

Cox²,

Herman³

et al. 1997

Antimicrob Agents Chemother

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Fluconazole, an inhibitor of certain human cytochrome P-450 isozymes, is used for the prevention and treatment of a broad range of fungal infections that predominantly affect immunocompromised individuals. This study evaluated the influence of fluconazole on the steady-state pharmacokinetics of delavirdine, a nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase, in 13 HIV-1-infected patients with CD4 counts ranging from 186 to 480/mm3. Both the control group (n = 5) and the fluconazole group (n = 8) received 300 mg of delavirdine mesylate every 8 h for 30 days; subjects in the fluconazole group took a 400-mg, once-daily dose of fluconazole on study days 16 to 30. Harvested plasma from serial blood samples collected on days 15, 16, and 30 were assayed for concentrations of delavirdine and its N-desalkyl metabolite by a reversed-phase high-pressure liquid chromatography (HPLC) method. Blood samples obtained on days 16 and 30 were also assayed for fluconazole by HPLC. Delavirdine mesylate alone and in combination with fluconazole was well tolerated. There were no significant differences (P > 0.16) in delavirdine pharmacokinetic parameters between treatment groups on day 15 or day 30. After coadministration of fluconazole and delavirdine mesylate for 2 weeks (day 30), no significant differences (P > 0.058) were observed in any delavirdine pharmacokinetic parameters relative to those after receiving delavirdine mesylate alone (day 15) after in the fluconazole group. Fluconazole pharmacokinetic parameters were similar to those previously reported for healthy volunteers and HIV-positive patients. On the basis of these findings, fluconazole and delavirdine mesylate may be taken concurrently without adjustment of the dose of either drug.

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Ketoconazole and Fluconazole Drug Interactions

Cited by 31 publications

References 48 publications

In Vitro and in Vivo Drug Interactions Involving Human Cyp3a

In Vitro and in Vivo Drug Interactions Involving Human Cyp3a

Gastric Function in the Elderly: Effects on Absorption of Ketoconazole

Effect of fluconazole on the steady-state pharmacokinetics of delavirdine in human immunodeficiency virus-positive patients

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