Abstract
The pharmacokinetics of amphotericin B were studied in two patients at the conclusion of long-term therapy for disseminated histoplasmosis. The distribution kinetics of this drug were adequately described by a three-compartment mamillary model with a total distribution volume averaging 4 liters/kg. The elimination phase half-life of amphotericin B was approximately 15 days, reflecting slow release of amphotericin B from a peripheral compartment. In accordance with previous reports, renal excretion accounted for only 3% of total amphotericin B elimination. The pharmacokinetic model for one of the patients also was used to compare the simulated amphotericin B serum levels that would be expected if initial therapy followed two recommended regimens.
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Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Atkinson A. J., Jr, Bindschadler D. D. Pharmacokinetics of intrathecally administered amphotericin B. Am Rev Respir Dis. 1969 Jun;99(6):917–924. doi: 10.1164/arrd.1969.99.6.917. [DOI] [PubMed] [Google Scholar]
- Bennett J. E. Chemotherapy of systemic mycoses (first of two parts). N Engl J Med. 1974 Jan 3;290(1):30–32. doi: 10.1056/NEJM197401032900107. [DOI] [PubMed] [Google Scholar]
- Bindschadler D. D., Bennett J. E. A pharmacologic guide to the clinical use of amphotericin B. J Infect Dis. 1969 Oct;120(4):427–436. doi: 10.1093/infdis/120.4.427. [DOI] [PubMed] [Google Scholar]
- Block E. R., Bennett J. E., Livoti L. G., Klein W. J., Jr, MacGregor R. R., Henderson L. Flucytosine and amphotericin B: hemodialysis effects on the plasma concentration and clearance. Studies in man. Ann Intern Med. 1974 May;80(5):613–617. doi: 10.7326/0003-4819-80-5-613. [DOI] [PubMed] [Google Scholar]
- Butler W. T., Cotlove E. Increased permeability of human erythrocytes induced by amphotericin B. J Infect Dis. 1971 Apr;123(4):341–350. doi: 10.1093/infdis/123.4.341. [DOI] [PubMed] [Google Scholar]
- Drutz D. J., Spickard A., Rogers D. E., Koenig M. G. Treatment of disseminated mycotic infectioons. A new approach to amphotericin B therapy. Am J Med. 1968 Sep;45(3):405–418. doi: 10.1016/0002-9343(68)90075-2. [DOI] [PubMed] [Google Scholar]
- Feldman H. A., Hamilton J. D., Gutman R. A. Amphotericin B therapy in an anephric patient. Antimicrob Agents Chemother. 1973 Sep;4(3):302–305. doi: 10.1128/aac.4.3.302. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fields B. T., Jr, Bates J. H., Abernathy R. S. Amphotericin B serum concentrations during therapy. Appl Microbiol. 1970 Jun;19(6):955–959. doi: 10.1128/am.19.6.955-959.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jusko W. J., Gretch M. Plasma and tissue protein binding of drugs in pharmacokinetics. Drug Metab Rev. 1976;5(1):43–140. doi: 10.3109/03602537608995839. [DOI] [PubMed] [Google Scholar]
- LOURIA D. B. Some aspects of the absorption, distribution, and excretion of amphotericin B in man. Antibiotic Med Clin Ther (New York) 1958 May;5(5):295–301. [PubMed] [Google Scholar]
- Larsen P. R., Atkinson A. J., Jr, Wellman H. N., Goldsmith R. E. The effect of diphenylhydantoin on thyroxine metabolism in man. J Clin Invest. 1970 Jun;49(6):1266–1279. doi: 10.1172/JCI106339. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perrier D., Gibaldi M. Clearance and biologic half-life as indices of intrinsic hepatic metabolism. J Pharmacol Exp Ther. 1974 Oct;191(1):17–24. [PubMed] [Google Scholar]