Disposition of ketoconazole, an oral antifungal, in humans

C. Brass, John N Galgiani, T. F. Blaschke, R. Defelice, R. A. O'Reilly, D. A. Stevens

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

The pharmacology of ketoconazole was studied in patients with fungal infections. After administration of 50-, 100-, and 200-mg doses of ketoconazole, there was a linear increase in the area under the curve of serum concentrations; this was not apparent when higher doses of ketoconazole were given. An increase in the area under the curve occurred in patients receiving 200 mg daily who were restudied after 1 to 12 months of therapy. However, normalized area under the curve appeared to decrease after higher doses were administered chronically. The half life ranged from 2.0 to 3.3 h. Peak serum concentrations up to 50 μg/ml were detected in this study, and potentially therapeutic concentrations were detectable up to 26 h after high doses. Ketoconazole penetrated the saliva and inflamed joint fluid and meninges, although variably, and could be demonstrated in some other tissue compartments. In the presence of renal failure, ketoconazole disposition was not altered, whereas in the presence of hepatic insufficiency, an alteration in disposition was suggested. The interactions of ketoconazole and other drugs were studied. Of note, antacids did not significantly affect ketoconazole pharmacokinetics (nor did meals), and ketoconazole and warfarin did not appear to affect the pharmacokinetics of the other.

Original languageEnglish (US)
Pages (from-to)151-158
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Volume21
Issue number1
StatePublished - 1982
Externally publishedYes

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Ketoconazole
Area Under Curve
Pharmacokinetics
Hepatic Insufficiency
Meninges
Antacids
Mycoses
Warfarin
Serum
Saliva
Renal Insufficiency
Half-Life
Meals
Joints
Pharmacology
Therapeutics

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Brass, C., Galgiani, J. N., Blaschke, T. F., Defelice, R., O'Reilly, R. A., & Stevens, D. A. (1982). Disposition of ketoconazole, an oral antifungal, in humans. Antimicrobial Agents and Chemotherapy, 21(1), 151-158.

Disposition of ketoconazole, an oral antifungal, in humans. / Brass, C.; Galgiani, John N; Blaschke, T. F.; Defelice, R.; O'Reilly, R. A.; Stevens, D. A.

In: Antimicrobial Agents and Chemotherapy, Vol. 21, No. 1, 1982, p. 151-158.

Research output: Contribution to journalArticle

Brass, C, Galgiani, JN, Blaschke, TF, Defelice, R, O'Reilly, RA & Stevens, DA 1982, 'Disposition of ketoconazole, an oral antifungal, in humans', Antimicrobial Agents and Chemotherapy, vol. 21, no. 1, pp. 151-158.
Brass C, Galgiani JN, Blaschke TF, Defelice R, O'Reilly RA, Stevens DA. Disposition of ketoconazole, an oral antifungal, in humans. Antimicrobial Agents and Chemotherapy. 1982;21(1):151-158.
Brass, C. ; Galgiani, John N ; Blaschke, T. F. ; Defelice, R. ; O'Reilly, R. A. ; Stevens, D. A. / Disposition of ketoconazole, an oral antifungal, in humans. In: Antimicrobial Agents and Chemotherapy. 1982 ; Vol. 21, No. 1. pp. 151-158.
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