التفاصيل البيبلوغرافية
| العنوان: |
Population pharmacokinetics of meropenem in critically ill children with different renal functions. |
| المؤلفون: |
Rapp, Mélanie1,2,3 mehdi.oualha@aphp.fr, Urien, Saïk1,2, Foissac, Frantz1,2, Béranger, Agathe2,3, Bouazza, Naïm1,2, Benaboud, Sihem2,4, Bille, Emmanuelle5, Zheng, Yi2,3, Gana, Inès2,3, Moulin, Florence3, Lesage, Fabrice3, Renolleau, Sylvain3, Tréluyer, Jean Marc1,2,4, Hirt, Déborah2,4, Oualha, Mehdi2,3 |
| المصدر: |
European Journal of Clinical Pharmacology. Jan2020, Vol. 76 Issue 1, p61-71. 11p. 4 Charts, 4 Graphs. |
| مصطلحات موضوعية: |
*KIDNEY physiology, *BACTERIAL diseases, *BODY weight, *CRITICALLY ill, *DRUG administration, *GLOMERULAR filtration rate, *HEMODIALYSIS, *HIGH performance liquid chromatography, *MICROBIAL sensitivity tests, *PATIENTS, *STATISTICAL models, *MEROPENEM, *CHILDREN |
| مستخلص: |
Purpose: We aimed to develop a meropenem population pharmacokinetic (PK) model in critically ill children and simulate dosing regimens in order to optimize patient exposure. Methods: Meropenem plasma concentration was quantified by high-performance liquid chromatography. Meropenem PK was investigated using a non-linear mixed-effect modeling approach. Results: Forty patients with an age of 16.8 (1.4–187.2) months, weight of 9.1 (3.8–59) kg, and estimated glomerular filtration rate (eGFR) of 151 (19–440) mL/min/1.73 m2 were included. Eleven patients received continuous replacement renal therapy (CRRT). Concentration-time courses were best described by a two-compartment model with first-order elimination. Body weight (BW), eGFR, and CRRT were covariates explaining the between-subject variabilities on central/peripheral volume of distribution (V1/V2), inter-compartment clearance (Q), and clearance (CL): V1i = V1pop × (BW/70)1, Qi = Qpop × (BW/70)0.75, V2i = V2pop × (BW/70)1, CLi = (CLpop × (BW/70)0.75) × (eGFR/100)0.378) for patients without CRRT and CLi = (CLpop × (BW/70)0.75) × 0.9 for patients with CRRT, where CLpop, V1pop, Qpop, and V2pop are 6.82 L/h, 40.6 L, 1 L/h, and 9.2 L respectively normalized to a 70-kg subject. Continuous infusion, 60 and 120 mg/kg per day, is the most adequate dosing regimen to attain the target of 50% fT > MIC and 100% fT > MIC for patients infected by bacteria with high minimum inhibitory concentration (MIC) value (> 4 mg/L) without risk of accumulation except in children with severe renal failure. Conclusion: Continuous infusion allows reaching the fT > MIC targets safely in children with normal or increased renal clearance. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |
