Pharmacokinetics of caspofungin acetate to guide optimal dosing in cats
| Autor: | David J. R. Foster, Andrew J. McLachlan, Jana Leshinsky, Vanessa R. Barrs, Ross Norris |
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| Přispěvatelé: | Leshinsky, Jana, McLachlan, Andrew, Foster, David JR, Norris, Ross, Barrs, Vanessa R |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Antifungal Agents Speciation Invasive Species lcsh:Medicine Pharmacology Cat Diseases Echinocandins chemistry.chemical_compound Caspofungin Medicine and Health Sciences polycyclic compounds caspofungin lcsh:Science Mammals education.field_of_study Multidisciplinary Pharmaceutics Simulation and Modeling Fungal Diseases Adjustment of Dosage at Steady State Caspofungin Acetate Infectious Diseases Vertebrates Female Research Article Evolutionary Processes 030106 microbiology Population Cmax Biology Research and Analysis Methods fungal rhinosinusitis Loading dose Lipopeptides 03 medical and health sciences Cmin Dose Prediction Methods Species Colonization Pharmacokinetics Cryptic Speciation Animals Aspergillosis Dosing education Evolutionary Biology Dose-Response Relationship Drug Aspergillus fumigatus cats Ecology and Environmental Sciences lcsh:R Organisms Biology and Life Sciences chemistry Amniotes Cats lcsh:Q |
| Zdroj: | PLoS ONE, Vol 12, Iss 6, p e0178783 (2017) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Cats are the most common mammal to develop invasive fungal rhinosinusitis caused by cryptic species in Aspergillus section Fumigati that are resistant to azoles but susceptible to caspofungin. In this study nonlinear mixed-effects pharmacokinetic modeling and simulation was used to investigate caspofungin pharmacokinetics and explore dosing regimens in cats using caspofungin minimum effective concentrations (MECs). Plasma concentrations in healthy cats were determined using HPLC-MS/MS after administration of a single and seven consecutive daily intravenous doses of 1 mg/kg caspofungin. In the final pharmacokinetic model an optimum maximum concentration (Cmax): MEC ratio of 10-20 was used to guide caspofungin efficacy. Simulations were performed for dosing regimens (doses 0.25-2 mg/kg and 6-72 h dosing intervals) with and without inclusion of a loading dose. Using a 1 mg/kg dose Cmax first dose was 14.8 μg/mL, Cmax at steady state was 19.8 μg/mL, Cmin was 5 μg/mL and Cmax: MEC was >20 in 42.6% of cats after multiple doses. An optimal Cmax: MEC ratio was achieved in caspofungin simulations using 0.75 mg/kg q 24 h or 1 mg/kg q 72h. However, at 1 mg/kg q 72h, Cmin was < MEC ( 2.5 μg/mL for 98% of the population. Based on the modeling data this dosing regimen is likely to achieve target therapeutic concentrations, meet the proposed Cmax: MEC window and provide consistent exposure between doses. Refereed/Peer-reviewed |
| Databáze: | OpenAIRE |
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