Objective: To determine the pharmacokinetic model that most adequately describes the pharmacokinetics of flucytosine in ICU patients. Methods: Retrospective analysis of 353 plasma levels of 53 ICU patients treated with intravenous flucytosine for systemic infections with Candida, Cryptoccoccus and Aspergillus species. Trough as well as peak levels were measured by high performance liquid chromatography. Pharmacokinetic parameters were calculated by Bayesian estimation using the program MW/PHARM (Mediware, Groningen, The Netherlands). The choice of the model that most adequately describes the pharmacokinetics of flucytosine was done by minimum Akaike Information Criterion estimation (MAICE). Three models were tested: a two compartment model with renal clearance, an one compartment model with renal and metabolic clearance and an one compartment model with only renal clearance. Results: In 94% of the patients the calculated Akaike Information Criterion was lowest for the one compartment model with only renal clearance. Average (SD) pharmacokinetic parameters for this model were: kelr = 0.00094 (0.00052) L/h/(ml/min) V1 = 0.89920 (0.41216) L/kg. Conclusion: An one compartment model with renal clearance can be used for the optimisation of flucytosine dosage regimen in ICU patients, which is relevant to avoid development of resistance and toxicity.
Full conference title:
38th Interscience Conference on Antimicrobial Agents and Chemotherapy
- ICAAC 38th