Population pharmacokinetic modeling of the influence of chronic and acute biofilm-forming Pseudomonas aeruginosa lung infection on ciprofloxacin free pulmonary and epithelial lining fluid concentrations.

Lock, Graziela De Araujo; Helfer, Victória Etges; Dias, Bruna Bernar; Torres, Bruna Gaelzer Silva; De Araújo, Bibiana Verlindo; Dalla Costa, Teresa

Lock, Graziela De Araujo; Helfer, Victória Etges; Dias, Bruna Bernar; Torres, Bruna Gaelzer Silva; De Araújo, Bibiana Verlindo; Dalla Costa, Teresa.

Afiliação

Lock GA; Pharmacokinetics and PK/PD Modeling Laboratory, Pharmaceutical Sciences Graduate Program, Faculty of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Helfer VE; Pharmacokinetics and PK/PD Modeling Laboratory, Pharmaceutical Sciences Graduate Program, Faculty of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Dias BB; Pharmacokinetics and PK/PD Modeling Laboratory, Pharmaceutical Sciences Graduate Program, Faculty of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Torres BGS; Pharmacokinetics and PK/PD Modeling Laboratory, Pharmaceutical Sciences Graduate Program, Faculty of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
De Araújo BV; Pharmacokinetics and PK/PD Modeling Laboratory, Pharmaceutical Sciences Graduate Program, Faculty of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Dalla Costa T; Pharmacokinetics and PK/PD Modeling Laboratory, Pharmaceutical Sciences Graduate Program, Faculty of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: dalla.costa@ufrgs.br.

Eur J Pharm Sci ; 189: 106546, 2023 Oct 01.

Article em En | MEDLINE | ID: mdl-37517670

RESUMO

We previously reported that ciprofloxacin (CIP) free lung interstitial concentrations are decreased by biofilm-forming Pseudomonas aeruginosa pulmonary chronic (14 d) infection. To get a better understanding on the influence of infection on CIP lung distribution, in the present study free lung interstitial fluid and epithelial lining fluid (ELF) concentrations were determined by microdialysis in biofilm-forming P. aeruginosa acutely (2 d) and chronically infected (14 d) Wistar rats following CIP 20 mg/kg i.v. bolus dosing. A popPK model was developed, using NONMEM® (version 7.4.3) with FOCE+I, with plasma data described as a three-compartment model with first-order elimination. For lung data inclusion, the model was expanded to four compartments and ELF concentrations were described as a fraction of lung levels estimated as a distribution factor (ƒD). Acute infection had a minor impact on plasma and lung CIP distribution and both infection stages did not alter ELF drug penetration. Probability of target attainment of ƒAUC0-24/MIC ≥ 90 using 20 mg q8h, equivalent to 400 mg q8h in humans, showed that CIP free concentrations in plasma are adequate to successfully treat lung infections. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection.

Assuntos

Ciprofloxacina; Infecções por Pseudomonas; Humanos; Ratos; Animais; Antibacterianos; Pseudomonas aeruginosa; Infecção Persistente; Ratos Wistar; Infecções por Pseudomonas/tratamento farmacológico; Pulmão; Biofilmes; Testes de Sensibilidade Microbiana

Palavras-chave

Ciprofloxacin; Epithelial lining fluid; Lung infection; Microdialysis; Population pharmacokinetic model; Pseudomonas aeruginosa

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções por Pseudomonas / Ciprofloxacina Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Eur J Pharm Sci Assunto da revista: FARMACIA / FARMACOLOGIA / QUIMICA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda

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