Lack of pharmacokinetic and pharmacodynamic interactions between ketoconazole and prednisolone
The effects of ketoconazole on the pharmacokinetics and pharmacodynamics of intravenous prednisolone (14.8 mg) were assessed in six healthy volunteers. Subjects were studied with and without receiving ketoconazole, 200 mg orally for 6 days. The addition of ketoconazole did not significantly change t...
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Published in | Clinical pharmacology and therapeutics Vol. 49; no. 5; p. 558 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.05.1991
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Abstract | The effects of ketoconazole on the pharmacokinetics and pharmacodynamics of intravenous prednisolone (14.8 mg) were assessed in six healthy volunteers. Subjects were studied with and without receiving ketoconazole, 200 mg orally for 6 days. The addition of ketoconazole did not significantly change the clearance (96 +/- 11 versus 90 +/- 11 ml/hr/kg), mean residence time (4.29 +/- 0.43 versus 4.45 +/- 0.59 hours), volume of distribution (0.41 +/- 0.02 versus 0.40 +/- 0.02 L/kg), or plasma protein binding characteristics of prednisolone. The suppressive effects of prednisolone on serum cortisol, blood basophil, and helper T lymphocyte values, assessed by the ratio of the area under the curve (AUC) after prednisolone administration to the baseline AUC, was not altered significantly by ketoconazole. The 50% inhibitory concentration values derived from pharmacodynamic models developed to describe the direct suppressive effects of corticosteroids indicated no alteration in intrinsic sensitivity in the presence of ketoconazole. Ketoconazole does not appear to alter the pharmacokinetics or the pharmacodynamic response patterns of selected direct suppression effects of single low doses of prednisolone. |
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AbstractList | The effects of ketoconazole on the pharmacokinetics and pharmacodynamics of intravenous prednisolone (14.8 mg) were assessed in six healthy volunteers. Subjects were studied with and without receiving ketoconazole, 200 mg orally for 6 days. The addition of ketoconazole did not significantly change the clearance (96 +/- 11 versus 90 +/- 11 ml/hr/kg), mean residence time (4.29 +/- 0.43 versus 4.45 +/- 0.59 hours), volume of distribution (0.41 +/- 0.02 versus 0.40 +/- 0.02 L/kg), or plasma protein binding characteristics of prednisolone. The suppressive effects of prednisolone on serum cortisol, blood basophil, and helper T lymphocyte values, assessed by the ratio of the area under the curve (AUC) after prednisolone administration to the baseline AUC, was not altered significantly by ketoconazole. The 50% inhibitory concentration values derived from pharmacodynamic models developed to describe the direct suppressive effects of corticosteroids indicated no alteration in intrinsic sensitivity in the presence of ketoconazole. Ketoconazole does not appear to alter the pharmacokinetics or the pharmacodynamic response patterns of selected direct suppression effects of single low doses of prednisolone. |
Author | Jusko, W J Ludwig, E A Middleton, Jr, E Yamashita, S K |
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BackLink | https://www.ncbi.nlm.nih.gov/pubmed/1827622$$D View this record in MEDLINE/PubMed |
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Snippet | The effects of ketoconazole on the pharmacokinetics and pharmacodynamics of intravenous prednisolone (14.8 mg) were assessed in six healthy volunteers.... |
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SubjectTerms | Adult Analysis of Variance Basophils - metabolism Blood Proteins - metabolism Circadian Rhythm Drug Evaluation Drug Interactions Histamine - blood Humans Hydrocortisone - blood Ketoconazole - blood Ketoconazole - pharmacokinetics Ketoconazole - pharmacology Leukocyte Count Male Prednisolone - blood Prednisolone - pharmacokinetics Prednisolone - pharmacology Protein Binding T-Lymphocytes, Helper-Inducer - cytology |
Title | Lack of pharmacokinetic and pharmacodynamic interactions between ketoconazole and prednisolone |
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