ArticleAntimicrobial agents and chemotherapy2009
Combination therapy of advanced invasive pulmonary aspergillosis in transiently neutropenic rats using human pharmacokinetic equivalent doses of voriconazole and anidulafungin.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Bronchopulmonary disposition of intravenous voriconazole and anidulafungin given in combination to healthy adults.Antimicrobial agents and chemotherapy · 2009Trial
- Comparative Pharmacodynamics of Echinocandins against Aspergillus fumigatus Using anAntimicrobial agents and chemotherapy · 2021Article
- ASP2397 Is a Novel Natural Compound That Exhibits Rapid and Potent Fungicidal Activity againstAntimicrobial agents and chemotherapy · 2019Article
- Activity of Combined Antifungal Agents Against Multidrug-Resistant Candida glabrata Strains.Mycopathologia · 2017Article
- Article
- Antifungal pharmacokinetics and pharmacodynamics.Cold Spring Harbor perspectives in medicine · 2014Review
- Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology.The Journal of antimicrobial chemotherapy · 2014Review
- Discrimination of Aspergillus lentulus from Aspergillus fumigatus by Raman spectroscopy and MALDI-TOF MS.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2014Article
- Efficacy of combination therapy of triazole and echinocandin in treatment of invasive aspergillosis: a systematic review of animal and human studies.Journal of thoracic disease · 2014Article
- Efficacy of the combination of voriconazole and caspofungin in experimental pulmonary aspergillosis by different Aspergillus species.Mycopathologia · 2014Article
- Impact of in vivo triazole and echinocandin combination therapy for invasive pulmonary aspergillosis: enhanced efficacy against Cyp51 mutant isolates.Antimicrobial agents and chemotherapy · 2013Article
- Amphotericin B- and voriconazole-echinocandin combinations against Aspergillus spp.: Effect of serum on inhibitory and fungicidal interactions.Antimicrobial agents and chemotherapy · 2013Article
- In vitro interaction of voriconazole and anidulafungin against triazole-resistant Aspergillus fumigatus.Antimicrobial agents and chemotherapy · 2013Article
- Pharmacodynamics of anidulafungin against clinical Aspergillus fumigatus isolates in a nonneutropenic murine model of disseminated aspergillosis.Antimicrobial agents and chemotherapy · 2013Article
- Combination of voriconazole and anidulafungin for treatment of triazole-resistant aspergillus fumigatus in an in vitro model of invasive pulmonary aspergillosis.Antimicrobial agents and chemotherapy · 2012Article
- In vitro combination of anidulafungin and voriconazole against intrinsically azole-susceptible and -resistant Aspergillus spp.Antimicrobial agents and chemotherapy · 2012Article
- Combined therapy of voriconazole and anidulafungin in murine infections by Aspergillus flavus.Mycopathologia · 2012Article
- Drosophila melanogaster as a model organism for invasive aspergillosis.Methods in molecular biology (Clifton, N.J.) · 2012Article
- Current role of echinocandins in the management of invasive aspergillosis.Current infectious disease reports · 2011Article
- Pros and Cons of Extrapolating Animal Data on Antifungal Pharmacodynamics to Humans.Current fungal infection reports · 2011Article
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
At present, voriconazole (VOR) is the drug of first choice for treating invasive pulmonary aspergillosis (IPA). However, particularly in advanced stages of disease and in the severely immunocompromised host, the mortality remains substantial. The combination of VOR with an echinocandin may improve the therapeutic outcome. We investigate here whether combining VOR and anidulafungin (ANI) in advanced IPA in transiently neutropenic rats results in a higher therapeutic efficacy. Since VOR is metabolized more rapidly in rodents than in humans, dosage adjustment for VOR is necessary to obtain an area under the plasma concentration-time curve (AUC) in rodents that is equivalent to that of humans. In this study, the pharmacokinetics of VOR and ANI in rats were elucidated, and dosage schedules were applied that produced AUCs similar to those of humans. The developed dose schedules were well tolerated by the rats, without effects on renal and hepatic functions. VOR showed excellent efficacy in early IPA (100% rat survival). In advanced IPA, VOR was less efficacious (50% rat survival), whereas a significant decrease in galactomannan concentrations in lungs and sera was found in surviving rats. ANI administered in advanced IPA resulted in 22% rat survival, and the serum concentrations of fungal galactomannan were slightly but not significantly decreased. The addition of ANI to VOR did not result in significantly increased therapeutic efficacy in advanced IPA, resulting in 67% rat survival and a significant decrease in galactomannan concentration in serum. In conclusion, VOR monotherapy is therapeutically effective in the treatment of advanced-stage IPA and superior to the use of ANI. Combining both agents does not significantly improve the therapeutic outcome.
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