Abstract | BACKGROUND AND OBJECTIVE: METHODS:
Meropenem plasma concentration was quantified by high-performance liquid chromatography. Meropenem pharmacokinetics was investigated using a non-linear mixed-effect modeling approach. Monte Carlo simulations were performed to compute the optimal scheme of administration, according to the target of a 100% inter-dose interval time in which concentration is one to four times above the minimum inhibitory concentration (100% fT>1-4×MIC). RESULTS: A total of 27 patients with a median age of 4 [interquartile range 0-11] years, a median body weight of 16 [range 7-35] kg receiving continuous renal replacement therapy were included. Concentration-time courses were best described by a one-compartment model with first-order elimination. Body weight (BW) produced significant effects on volume of distribution (V) and BW and continuous renal replacement therapy effluent flow rate (Qeff) produced significant effects on clearance (CL): [Formula: see text] and [Formula: see text], where Vpop and CLpop estimates were 32.5 L and 5.88 L/h, respectively, normalized to a 70-kg BW and median Qeff at 1200 mL/h. Using this final model and Monte Carlo simulations, for patients with Qeff over 1200 mL/h, meropenem continuous infusion was adequate in most cases to attain 100% fT>1-4xMIC. For bacterial infections with a low minimum inhibitory concentration (≤2 mg/L), meropenem intermitent administration was appropriate for patients weighing more than 20 kg with Qeff <500 mL/h and for patients weighing more than 10 kg with Qeff <100 mL/h. CONCLUSIONS:
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Authors | Michael Thy, Saik Urien, Naim Bouazza, Frantz Foissac, Inès Gana, Emmanuelle Bille, Agathe Béranger, Julie Toubiana, Romain Berthaud, Fabrice Lesage, Sylvain Renolleau, Jean-Marc Tréluyer, Sihem Benaboud, Mehdi Oualha |
Journal | Clinical pharmacokinetics
(Clin Pharmacokinet)
Vol. 61
Issue 11
Pg. 1609-1621
(11 2022)
ISSN: 1179-1926 [Electronic] Switzerland |
PMID | 36251162
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG. |
Chemical References |
- Meropenem
- Anti-Bacterial Agents
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Topics |
- Child
- Humans
- Infant, Newborn
- Infant
- Child, Preschool
- Meropenem
(pharmacokinetics)
- Continuous Renal Replacement Therapy
- Critical Illness
(therapy)
- Anti-Bacterial Agents
(pharmacokinetics)
- Microbial Sensitivity Tests
- Body Weight
- Renal Replacement Therapy
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