Pharmacokinetics of Liposomal Amphotericin B (Ambisome) in Critically Ill Patients

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 1997 Jun 1

PMID 9174183

Citations 27

Authors

V Heinemann

D Bosse

U Jehn

B Kahny

K Wachholz

A Debus

P Scholz

H J Kolb

W Wilmanns

Affiliations

Soon will be listed here.

Abstract

The liposomal formulation of amphotericin B (AmBisome) greatly reduces the acute and chronic side effects of the parent drug. The present study describes the pharmacokinetic characteristics of AmBisome applied to 10 patients at a dose of 2.8 to 3.0 mg/kg of body weight and compares them to the pharmacokinetics observed in 6 patients treated with amphotericin B deoxycholate at the standard dose of 1.0 mg/kg. Interpatient variabilities of amphotericin B peak concentrations (Cmax) and areas under concentration-time curves (AUC) were 8- to 10-fold greater for patients treated with AmBisome than for patients treated with amphotericin B deoxycholate. At the threefold greater dose of AmBisome, median Cmaxs were 8.4-fold higher (14.4 versus 1.7 microg/ml) and median AUCs exceeded those observed with amphotericin B deoxycholate by 9-fold. This was in part explained by a 5.7-fold lower volume of distribution (0.42 liters/kg) in AmBisome-treated patients. The elimination of amphotericin B from serum was biphasic for both formulations. However, the apparent half-life of elimination was twofold shorter for AmBisome (P = 0.03). Neither hemodialysis nor hemofiltration had a significant impact on AmBisome pharmacokinetics as analyzed in one patient. In conclusion, the liposomal formulation of amphotericin B significantly (P = 0.001) reduces the volume of drug distribution, thereby allowing for greater drug concentrations in serum. The low toxicity of AmBisome therefore cannot readily be explained by its serum pharmacokinetics.

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References

Sculier J, COUNE A, Meunier F, Brassinne C, Laduron C, Hollaert C . Pilot study of amphotericin B entrapped in sonicated liposomes in cancer patients with fungal infections. Eur J Cancer Clin Oncol. 1988; 24(3):527-38. DOI: 10.1016/s0277-5379(98)90033-5. View

Burch P, Karp J, Merz W, Kuhlman J, Fishman E . Favorable outcome of invasive aspergillosis in patients with acute leukemia. J Clin Oncol. 1987; 5(12):1985-93. DOI: 10.1200/JCO.1987.5.12.1985. View

Gondal J, Swartz R, Rahman A . Therapeutic evaluation of free and liposome-encapsulated amphotericin B in the treatment of systemic candidiasis in mice. Antimicrob Agents Chemother. 1989; 33(9):1544-8. PMC: 172699. DOI: 10.1128/AAC.33.9.1544. View

Lopez-Berestein G, Bodey G, Fainstein V, Keating M, Frankel L, Zeluff B . Treatment of systemic fungal infections with liposomal amphotericin B. Arch Intern Med. 1989; 149(11):2533-6. View

Gallis H, Drew R, Pickard W . Amphotericin B: 30 years of clinical experience. Rev Infect Dis. 1990; 12(2):308-29. DOI: 10.1093/clinids/12.2.308. View

Joly V, Carbon C, Yeni P . Interactions of free and liposomal amphotericin B with renal proximal tubular cells in primary culture. J Pharmacol Exp Ther. 1990; 255(1):17-22. View

Anaissie E, Paetznick V, Proffitt R, Bodey G . Comparison of the in vitro antifungal activity of free and liposome-encapsulated amphotericin B. Eur J Clin Microbiol Infect Dis. 1991; 10(8):665-8. DOI: 10.1007/BF01975823. View

Gregoriadis G . Overview of liposomes. J Antimicrob Chemother. 1991; 28 Suppl B:39-48. DOI: 10.1093/jac/28.suppl_b.39. View

Proffitt R, Satorius A, Chiang S, Sullivan L, Adler-Moore J . Pharmacology and toxicology of a liposomal formulation of amphotericin B (AmBisome) in rodents. J Antimicrob Chemother. 1991; 28 Suppl B:49-61. DOI: 10.1093/jac/28.suppl_b.49. View

10.

Adler-Moore J, Chiang S, Satorius A, Guerra D, McAndrews B, McManus E . Treatment of murine candidosis and cryptococcosis with a unilamellar liposomal amphotericin B formulation (AmBisome). J Antimicrob Chemother. 1991; 28 Suppl B:63-71. DOI: 10.1093/jac/28.suppl_b.63. View

11.

BINDSCHADLER D, Bennett J . A pharmacologic guide to the clinical use of amphotericin B. J Infect Dis. 1969; 120(4):427-36. DOI: 10.1093/infdis/120.4.427. View

12.

Fields Jr B, Bates J, Abernathy R . Amphotericin B serum concentrations during therapy. Appl Microbiol. 1970; 19(6):955-9. PMC: 376832. DOI: 10.1128/am.19.6.955-959.1970. View

13.

Feldman H, Hamilton J, Gutman R . Amphotericin B therapy in an anephric patient. Antimicrob Agents Chemother. 1973; 4(3):302-5. PMC: 444546. DOI: 10.1128/AAC.4.3.302. View

14.

Lopez-Berestein G, Mehta R, Hopfer R, Mills K, Kasi L, Mehta K . Treatment and prophylaxis of disseminated infection due to Candida albicans in mice with liposome-encapsulated amphotericin B. J Infect Dis. 1983; 147(5):939-45. DOI: 10.1093/infdis/147.5.939. View

15.

Mehta R, Lopez-Berestein G, Hopfer R, Mills K, Juliano R . Liposomal amphotericin B is toxic to fungal cells but not to mammalian cells. Biochim Biophys Acta. 1984; 770(2):230-4. DOI: 10.1016/0005-2736(84)90135-4. View

16.

Christiansen K, Bernard E, Gold J, Armstrong D . Distribution and activity of amphotericin B in humans. J Infect Dis. 1985; 152(5):1037-43. DOI: 10.1093/infdis/152.5.1037. View

17.

Szoka Jr F, Milholland D, Barza M . Effect of lipid composition and liposome size on toxicity and in vitro fungicidal activity of liposome-intercalated amphotericin B. Antimicrob Agents Chemother. 1987; 31(3):421-9. PMC: 174744. DOI: 10.1128/AAC.31.3.421. View

18.

Meunier F, Prentice H, Ringden O . Liposomal amphotericin B (AmBisome): safety data from a phase II/III clinical trial. J Antimicrob Chemother. 1991; 28 Suppl B:83-91. DOI: 10.1093/jac/28.suppl_b.83. View

19.

Chopra R, Blair S, Strang J, Cervi P, Patterson K, Goldstone A . Liposomal amphotericin B (AmBisome) in the treatment of fungal infections in neutropenic patients. J Antimicrob Chemother. 1991; 28 Suppl B:93-104. DOI: 10.1093/jac/28.suppl_b.93. View

20.

Gray A, Morgan J . Liposomes in haematology. Blood Rev. 1991; 5(4):258-72. DOI: 10.1016/0268-960x(91)90017-7. View