Absorption of orally administered amphotericin B lozenges.

Ching, Michael S.; Raymond, Kenneth; Bury, Ross W.; Mashford, Maurice L.; Morgan, DJ

doi:10.1111/j.1365-2125.1983.tb02152.x

Cited by 30 publications

(20 citation statements)

References 5 publications

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“…Commercial amphotericin B oral suspension contains flavorings designed to overcome this problem, although it is reported that some patients find the taste disagreeable. Systemic absorption of orally administered amphotericin is reported to be minimal except after antineoplastic chemotherapy [47, 42,15], and systemic absorption was assessed in the current study. The minimal blood levels of amphotericin B seen in the current trial suggest minimal though measurable uptake of amphotericin B despite limited compliance with use of the rinse.…”

Section: Discussionmentioning

confidence: 99%

Topical polyene antifungals in hematopoietic cell transplant patients: tolerability and efficacy

Epstein

Truelove

Hanson-Huggins

et al. 2004

Support Care Cancer

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Ulcerative mucositis occurred in 84.6% of patients undergoing HCT, and no correlation was observed between the severity of mucositis and the presence of oral Candida and the severity of mucositis. Systemic and topical antifungal treatment resulted in a decrease in the number of colonized patients (54.8% before treatment; 23.1% during treatment); however, oral colonization was not eliminated. Tolerability of the oral rinse products was limited, with greater noncompliance in the amphotericin B than the nystatin group. Reports of altered taste appeared to be greater in the amphotericin B group. Minimal absorption of amphotericin B was seen following oral rinsing (serum levels 0.12-0.50 microg/ml), and no consistent changes in organism susceptibility to polyenes were seen. The results suggest that topical antifungal rinses may further control oropharyngeal colonization by Candida in patients on systemic antifungals receiving HCT, but the effect is limited by tolerability and reformulation and should be considered in order to increase compliance.

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Section: Discussionmentioning

confidence: 99%

Topical polyene antifungals in hematopoietic cell transplant patients: tolerability and efficacy

Epstein

Truelove

Hanson-Huggins

et al. 2004

Support Care Cancer

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“…DAMB therapy is associated with nephrotoxicity, central nervous system and liver damage, and side effects such as nausea and fever (23,34,35). AMB, with its inherent low solubility in water and many organic solvents, shows relatively poor bioavailability (11,12). In order to increase the therapeutic index of AMB and reduce its associated toxicity, new lipid-based formulations have been developed (1,3,33).…”

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confidence: 99%

Efficacy of Oral Cochleate-Amphotericin B in a Mouse Model of Systemic Candidiasis

Santangelo

Paderu

Delmas

et al. 2000

Antimicrob Agents Chemother

134

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Amphotericin B (AMB) remains the principal therapeutic choice for deep mycoses. However, its application is limited by toxicity and a route of administration requiring slow intravenous injection. An oral formulation of this drug is desirable to treat acute infections and provide prophylactic therapy for high-risk patients. Cochleates are a novel lipid-based delivery system that have the potential for oral administration of hydrophobic drugs. They are stable phospholipid-cation crystalline structures consisting of a spiral lipid bilayer sheet with no internal aqueous space. Cochleates containing AMB (CAMB) inhibit the growth of Candida albicans, and the in vivo therapeutic efficacy of CAMB administered orally was evaluated in a mouse model of systemic candidiasis. The results indicate that 100% of the mice treated at all CAMB doses, including a low dosage of 0.5 mg/kg of body weight/day, survived the experimental period (16 days). In contrast, 100% mortality was observed with untreated mice by day 12. The fungal tissue burden in kidneys and lungs was assessed in parallel, and a dose-dependent reduction in C. albicans from the kidneys was observed, with a maximum 3.5-log reduction in total cell counts at 2.5 mg/kg/day. However, complete clearance of the organism from the lungs, resulting in more than a 4-log reduction, was observed at the same dose. These results were comparable to a deoxycholate AMB formulation administered intraperitoneally at 2 mg/kg/day (P < 0.05). Overall, these data demonstrate that cochleates are an effective oral delivery system for AMB in a model of systemic candidiasis.The opportunistic fungal pathogen Candida albicans causes life-threatening infections among cancer patients, organ or bone marrow transplant recipients, and patients with congenital and acquired immunodeficiencies (4,14,17,24,28,29,32,43). Candida is the fourth leading cause of nosocomial bloodstream infections, accounting for 8% of all infections, and remains an important cause of morbidity and mortality in immunocompromised patients (7,28,31,32,43).Parenteral administration of amphotericin B (AMB), a polyene antibiotic with strong antifungal activity, remains the therapy of choice for systemic mycoses. It is highly hydrophobic and is commonly administrated as desoxycholate amphotericin (DAMB), a detergent micelle complex. AMB binds preferentially to ergosterol in fungal plasma membranes, although it also interacts with animal cell sterols such as cholesterol, which accounts for known toxicity (10, 35). DAMB therapy is associated with nephrotoxicity, central nervous system and liver damage, and side effects such as nausea and fever (23,34,35). AMB, with its inherent low solubility in water and many organic solvents, shows relatively poor bioavailability (11,12). In order to increase the therapeutic index of AMB and reduce its associated toxicity, new lipid-based formulations have been developed (1,3,33). These drug delivery systems, such as liposomal formulations, lipid complexes, lipid emulsions, and colloidal dispersion...

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“…The estimated absorbed fraction of conventional AmB in human was calculated to be 0.86% after a 2 g oral dose which is not effective 20 . Although the therapeutic levels can be reached by the administration of parenteral formulations, the high cost and the complications of injectable formulations limit their wide use.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and tissue distribution of amphotericin B following oral administration of three lipid-based formulations to rats

Ibrahim¹,

Gershkovich²,

Sivak³

et al. 2012

Drug Development and Industrial Pharmacy

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The objective of this study was to assess the pharmacokinetics and tissue distribution of amphotericin B (AmB) in rats following oral administration of three lipid-based formulations (iCo-009, iCo-010 and iCo-011). The lipid-based formulations were administered to rats at a dose of 10 mg/kg and blood samples were withdrawn at predose, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72 h, after which the animals were sacrificed and the body organs were collected for AmB quantification using a validated HPLC method. Plasma pharmacokinetics parameters were determined using non-compartmental analysis. The disappearance of AmB from plasma was the slowest following the administration of iCo-010 with MRT of 63 h followed by iCo-009 then iCo-011 (36 and 27 h). The AUC(0-24h) of iCo-009 and iCo-010 was 1.5-2-fold higher than that of iCo-011. The kidney exposure was comparable between iCo-009 and iCo-010 and was higher than that of iCo-011. The lung exposure was the highest following iCo-010 administration as compared to that of iCo-009. The distribution of AmB from plasma to tissues resulted in a high accumulation of AmB overtime with slow back-distribution to plasma. The pharmacokinetics profiles varied among the three formulations, despite the similarity in lipid composition between iCo-010 and iCo-011 and the presence of Peceol® as a common component in the formulations. The administration of oral iCo-010 could lead to higher steady state concentrations in the tissues after multiple dosing, which could lead to enhanced eradication of tissue borne fungal and parasitic infections.

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Absorption of orally administered amphotericin B lozenges.

Cited by 30 publications

References 5 publications

Topical polyene antifungals in hematopoietic cell transplant patients: tolerability and efficacy

Topical polyene antifungals in hematopoietic cell transplant patients: tolerability and efficacy

Efficacy of Oral Cochleate-Amphotericin B in a Mouse Model of Systemic Candidiasis

Pharmacokinetics and tissue distribution of amphotericin B following oral administration of three lipid-based formulations to rats

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