An Evaluation of Amphotericin B In Vitro and In Vivo in Mice Against Coccidioides Immitis and Candida Albicans, and Preliminary Observations Concerning the Administration of Amphotericin B to Man*

Halde, Carlyn; Newcomer, Victor D.; Wright, Edwin T.; Sternberg, Thomas H.

doi:10.1038/jid.1957.26

Cited by 59 publications

(17 citation statements)

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“…The level of susceptibility varied (18,19,25,27,28) as well as our own data, the antifungal action of amB versus C. immitis was not inhibited by complex, ill-defined organic media. The inhibitory action of amB at 0.5 ug/ ml noted by Halde et al (9) was achieved in synthetic broth containing asparagine, glucose, citrate, glycerol, and several salts (29); Huppert (personal communication) has noted MICs for 18 strains of C. immitis grown on synthetic yeast morphology agar (pH approximately 4.5) to be between 0.15 and 1.25 ,ug/ml. Thus, the MICs were in the same range with both the well-defined synthetic media and the complex organic media.…”

Section: Discussionmentioning

confidence: 99%

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Uniform Susceptibility of Various Strains of Coccidioides immitis to Amphotericin B

Collins

Pappagianis

1977

Antimicrob Agents Chemother

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The susceptibility of 12 strains of Coccidioides immitis to amphotericin B. (amB) was studied in vitro and in vivo. The minimal inhibitory concentration (MIC) of the mycelial phase of these strains was 0.078 to 0.16 ,ug/ml after 3 days of incubation, but by 15 days all strains were inhibited by 2.5 ,ug/ml. Mice infected intraperitoneally with these strains were sucessfully treated with 0.5 mg of amB per kg per day. These strains included several studied by others and which reportedly varied widely in susceptibility (MIC from 0.24 to 24.01 ,ug/ml) to amB. Four of these strains representing this putative broad range of susceptibility were used to infect mice intranasally. Regardless of infecting strain, mice were sucessfully treated with 0.38, 0.75, and 1.5 mg/kg, but 0.19 mg/kg was only partially effective. Thus, in vivo as well as in vitro there was a uniform response of C. immitis strains to amB.

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Section: Discussionmentioning

confidence: 99%

“…Halde et al (9) reported that three strains of C. immitis were inhibited by amB at 0.5 ,g/ml (the lowest dose tested) in synthetic asparagine broth after 10 days at 370C. Littman (18) treated a patient with chronic coccidioidal osteomyelitis with intravenous amB.…”

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confidence: 99%

Uniform Susceptibility of Various Strains of Coccidioides immitis to Amphotericin B

Collins

Pappagianis

1977

Antimicrob Agents Chemother

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“…per day. H a l d e et al (8) demonstrated that oral treatment with 12 mg. daily was effective even if therapy was delayed until 8 days after the onset o f infection. Eradi cation o f the fungus, however, was observed in only 50% o f animals even i f treatment was started within 48 hours o f infection.…”

Section: Amphotericin Bmentioning

confidence: 99%

The Treatment of Experimental Fungus Infections

Louria¹

1961

Chemotherapy

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“…Although its poor stability in the acidic gastric environment could be relatively easily addressed by, for example, by use of an enteric coating, the low solubility and poor membrane permeability of AmB present a significant challenge for researchers. The plasma concentrations of AmB following oral administration are very low in humans (Hofstra et al, 1982), rats (Robbie et al, 1999) and mice (Halde et al, 1957).…”

Section: Introductionmentioning

confidence: 99%

Synergistic enhancement of parasiticidal activity of amphotericin B using copaiba oil in nanoemulsified carrier for oral delivery: an approach for non‐toxic chemotherapy

Gupta

Jaiswal

Asthana

et al. 2015

British J Pharmacology

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BACKGROUND AND PURPOSEThe aim of this study was to devise a nanoemulsified carrier system (CopNEC) to improve the oral delivery of amphotericin B (AmB) by increasing its oral bioavailability and synergistically enhance its antileishmanial activity with copaiba oil (Cop). EXPERIMENTAL APPROACHThe AmB encapsulated NEC (CopNEC-AmB) comprised of Cop, d-α-tocopheryl polyethylene glycol 1000 succinate and phosphatidylcholine was prepared by high-pressure homogenization method. Stability study of CopNEC-AmB was carried out in simulated gastric fluid and simulated intestinal fluid. The CopNEC-AmB and plain AmB were compared as regards their in vitro antileishmanial activity, pharmacokinetics, organ distribution and toxicity. KEY RESULTSThe optimal CopNEC-AmB had a small globule size, low polydispersity index, high ζ potential and encapsulation efficiency. The high resolution transmission electron microscopy illustrated spherical particle geometry with homogeny in their sizes. The optimal CopNEC-AmB was found to be stable in gastrointestinal fluids showing insignificant changes in globule size and encapsulation efficiency. The AUC0-48 value of CopNEC-AmB in rats was significantly improved showing 7.2-fold higher oral bioavailability than free drug. The in vitro antileishmanial activity of CopNEC-AmB was significantly higher than that of the free drug as Cop synergistically enhanced the antileishmanial effect of AmB by causing drastic changes in the morphology of Leishmania parasite and rupturing its plasma membrane. The CopNEC-AmB showed significantly less haemolytic toxicity and cytotoxicity and did not change the histopathology of kidney tissues as compared with AmB alone. CONCLUSIONS AND IMPLICATIONSThis prototype CopNEC formulation showed improved bioavailability and had a non-toxic synergistic effect on the antileishmanial activity of AmB.

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An Evaluation of Amphotericin B In Vitro and In Vivo in Mice Against Coccidioides Immitis and Candida Albicans, and Preliminary Observations Concerning the Administration of Amphotericin B to Man*

Cited by 59 publications

References 1 publication

Uniform Susceptibility of Various Strains of Coccidioides immitis to Amphotericin B

Uniform Susceptibility of Various Strains of Coccidioides immitis to Amphotericin B

The Treatment of Experimental Fungus Infections

Synergistic enhancement of parasiticidal activity of amphotericin B using copaiba oil in nanoemulsified carrier for oral delivery: an approach for non‐toxic chemotherapy

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