Application of physiologically based pharmacokinetic modeling to predict the pharmacokinetics of telavancin in obesity with renal impairment.
Eur J Clin Pharmacol
; 77(7): 989-998, 2021 Jul.
Article
em En
| MEDLINE
| ID: mdl-33447912
ABSTRACT
PURPOSE:
U.S. Food and Drug Administration (FDA) recommended telavancin dosing is based on total body weight (TBW) but lacks adjusted regimens for obese subjects with varying renal function. Our aim was to develop a physiologically based pharmacokinetic (PBPK) model of telavancin to design optimized dosing regimens for obese patients with hospital-acquired pneumonia (HAP) and varying renal function.METHODS:
The PBPK model was verified using clinical pharmacokinetic (PK) data of telavancin in healthy populations with varying renal function and obese populations with normal renal function. Then, the PBPK model was applied to predict the PK in obese HAP patients with renal impairment (RI).RESULTS:
The fold error values of PK parameters (AUC, Cmax, Tmax) were all within 1.5. The telavancin AUC0-inf was predicted to increase 1.07-fold in mild RI, 1.23-fold in moderate RI, 1.41-fold in severe RI, and 1.57-fold in end-stage renal disease (ESRD), compared with that in obese HAP with normal renal function. The PBPK model combined with Monte Carlo simulations (MCS) suggested that dose adjustment based on a 750-mg-fixed dose could achieve effectiveness with reduced risk of toxicity, compared with current TBW-based dosing recommendations.CONCLUSION:
The PBPK simulation proposed that using TBW-based regimen in obesity with RI should be avoided. Dose recommendations in obesity from the PBPK model are 750 mg daily for normal renal function and mild RI, 610 mg daily for moderate RI, 530 mg daily for severe RI, and 480 mg daily for ESRD.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Insuficiência Renal
/
Pneumonia Associada a Assistência à Saúde
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Lipoglicopeptídeos
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Aminoglicosídeos
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Antibacterianos
/
Obesidade
Tipo de estudo:
Guideline
/
Health_economic_evaluation
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Humans
/
Male
Idioma:
En
Revista:
Eur J Clin Pharmacol
Ano de publicação:
2021
Tipo de documento:
Article