Tags

Type your tag names separated by a space and hit enter

In vivo distribution and therapeutic efficacy of a novel amphotericin B poly-aggregated formulation.
J Antimicrob Chemother. 2008 May; 61(5):1125-31.JA

Abstract

OBJECTIVES

The purpose of this investigation is the study of toxicity, in vivo distribution and therapeutic activity against candidiasis of poly-aggregated amphotericin B, in two different formulations: not microencapsulated (P-AMB) or incorporated in albumin microspheres (MP-AMB).

METHODS

The therapeutic efficacy and toxicity of amphotericin B formulations was studied in an immunocompetent murine model of systemic candidiasis. A pharmacokinetic study was also performed to measure the plasma, kidney, liver and spleen amphotericin B concentrations after administration of the three formulations to mice.

RESULTS

The acute toxicity of P-AMB in mice is lower than that of the conventional amphotericin B reference formulation (D-AMB). The 50% lethal doses were increased at least eight times. Intravenous bolus administration of doses up to 40 mg/kg of body weight of poly-aggregated amphotericin B, either P-AMB or MP-AMB, did not produce acute symptoms of toxicity. Interestingly, in the pharmacokinetic study, significant (P < 0.05) lower plasma and kidney amphotericin B concentrations and higher liver and spleen amphotericin B concentrations were achieved after poly-aggregated amphotericin B formulation (P-AMB and MP-AMB) administration in relation to the reference formulation (D-AMB). At high amphotericin B doses, no significant differences in efficacy (P > 0.05) were observed among the formulations (D-AMB, P-AMB and MP-AMB).

CONCLUSIONS

Although the efficacy in the candidiasis treatment was decreased as a consequence of amphotericin B aggregation, it can be compensated by the possibility of increasing the doses with lower nephrotoxicity. Moreover, due to its lower toxicity while maintaining its effectiveness, the poly-aggregated formulations (P-AMB and MP-AMB) have a better therapeutic index than the conventional formulation (D-AMB).

Authors+Show Affiliations

Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University, 28040 Madrid, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18285313

Citation

Espada, R, et al. "In Vivo Distribution and Therapeutic Efficacy of a Novel Amphotericin B Poly-aggregated Formulation." The Journal of Antimicrobial Chemotherapy, vol. 61, no. 5, 2008, pp. 1125-31.
Espada R, Valdespina S, Dea MA, et al. In vivo distribution and therapeutic efficacy of a novel amphotericin B poly-aggregated formulation. J Antimicrob Chemother. 2008;61(5):1125-31.
Espada, R., Valdespina, S., Dea, M. A., Molero, G., Ballesteros, M. P., Bolás, F., & Torrado, J. J. (2008). In vivo distribution and therapeutic efficacy of a novel amphotericin B poly-aggregated formulation. The Journal of Antimicrobial Chemotherapy, 61(5), 1125-31. https://doi.org/10.1093/jac/dkn048
Espada R, et al. In Vivo Distribution and Therapeutic Efficacy of a Novel Amphotericin B Poly-aggregated Formulation. J Antimicrob Chemother. 2008;61(5):1125-31. PubMed PMID: 18285313.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vivo distribution and therapeutic efficacy of a novel amphotericin B poly-aggregated formulation. AU - Espada,R, AU - Valdespina,S, AU - Dea,M A, AU - Molero,G, AU - Ballesteros,M P, AU - Bolás,F, AU - Torrado,J J, Y1 - 2008/02/19/ PY - 2008/2/21/pubmed PY - 2008/6/11/medline PY - 2008/2/21/entrez SP - 1125 EP - 31 JF - The Journal of antimicrobial chemotherapy JO - J Antimicrob Chemother VL - 61 IS - 5 N2 - OBJECTIVES: The purpose of this investigation is the study of toxicity, in vivo distribution and therapeutic activity against candidiasis of poly-aggregated amphotericin B, in two different formulations: not microencapsulated (P-AMB) or incorporated in albumin microspheres (MP-AMB). METHODS: The therapeutic efficacy and toxicity of amphotericin B formulations was studied in an immunocompetent murine model of systemic candidiasis. A pharmacokinetic study was also performed to measure the plasma, kidney, liver and spleen amphotericin B concentrations after administration of the three formulations to mice. RESULTS: The acute toxicity of P-AMB in mice is lower than that of the conventional amphotericin B reference formulation (D-AMB). The 50% lethal doses were increased at least eight times. Intravenous bolus administration of doses up to 40 mg/kg of body weight of poly-aggregated amphotericin B, either P-AMB or MP-AMB, did not produce acute symptoms of toxicity. Interestingly, in the pharmacokinetic study, significant (P < 0.05) lower plasma and kidney amphotericin B concentrations and higher liver and spleen amphotericin B concentrations were achieved after poly-aggregated amphotericin B formulation (P-AMB and MP-AMB) administration in relation to the reference formulation (D-AMB). At high amphotericin B doses, no significant differences in efficacy (P > 0.05) were observed among the formulations (D-AMB, P-AMB and MP-AMB). CONCLUSIONS: Although the efficacy in the candidiasis treatment was decreased as a consequence of amphotericin B aggregation, it can be compensated by the possibility of increasing the doses with lower nephrotoxicity. Moreover, due to its lower toxicity while maintaining its effectiveness, the poly-aggregated formulations (P-AMB and MP-AMB) have a better therapeutic index than the conventional formulation (D-AMB). SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/18285313/In_vivo_distribution_and_therapeutic_efficacy_of_a_novel_amphotericin_B_poly_aggregated_formulation_ DB - PRIME DP - Unbound Medicine ER -