Weerachai Chaijamorn1, Dhakrit Rungkitwattanakul2, Sutthiporn Pattharachayakul3, Wanchana Singhan4, Taniya Charoensareerat5, Nattachai Srisawat6. 1. Faculty of Pharmacy, Siam University, Bangkok, Thailand. Electronic address: weerachai.cha@siam.edu. 2. Department of Clinical and Administrative Pharmacy and Sciences Howard University College of Pharmacy, Washington, DC, USA. 3. Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla, Thailand. 4. Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand. 5. Faculty of Pharmacy, Siam University, Bangkok, Thailand. 6. Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Bangkok, Thailand; Excellence Center for Critical Care Nephrology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand; Critical Care Nephrology Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Academic of Science, Royal Society of Thailand, Bangkok, Thailand; Tropical Medicine Cluster, Chulalongkorn University, Bangkok, Thailand; Center for Critical Care Nephrology, The CRISMA Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Abstract
PURPOSES: To gather available meropenem pharmacokinetics and define drug dosing regimens for Asian critically ill patients receiving CRRT. METHODS: All necessary pharmacokinetic and pharmacodynamic data from Asian population were gathered to develop mathematic models with first order elimination. Meropenem concentration-time profiles were calculated to evaluate efficacy based on the probability of target attainment (PTA) of 40%fT>4MIC. A group of 5000 virtual patients was created and tested using Monte Carlo simulations for each dose in the models. The optimal dosing regimens were defined as the doses achieved at least 90% of the PTA. RESULTS: The recommended meropenem dosing regimen for Asian critically ill patients receiving CRRT with standard (20-25 mL/kg/h) and high (35 mL/kg/h) effluent rates was 750 mg q 8 h to manage Gram negative infections with expected MIC < 2 mg/L in virtual Asian patients. Some meropenem dosages from available clinical resources could not achieve the aforementioned target. The volume of distribution, body weights and nonrenal clearance significantly contributed to drug dosing adaptation especially in the specific population. CONCLUSIONS: A meropenem regimen of 750 mg q 8 h was recommended for Asian critically ill patients receiving 2 different CRRT modalities with standard and high effluent rates. Clinical validation of these results is needed.
PURPOSES: To gather available meropenem pharmacokinetics and define drug dosing regimens for Asian critically illpatients receiving CRRT. METHODS: All necessary pharmacokinetic and pharmacodynamic data from Asian population were gathered to develop mathematic models with first order elimination. Meropenem concentration-time profiles were calculated to evaluate efficacy based on the probability of target attainment (PTA) of 40%fT>4MIC. A group of 5000 virtual patients was created and tested using Monte Carlo simulations for each dose in the models. The optimal dosing regimens were defined as the doses achieved at least 90% of the PTA. RESULTS: The recommended meropenem dosing regimen for Asian critically illpatients receiving CRRT with standard (20-25 mL/kg/h) and high (35 mL/kg/h) effluent rates was 750 mg q 8 h to manage Gram negative infections with expected MIC < 2 mg/L in virtual Asian patients. Some meropenem dosages from available clinical resources could not achieve the aforementioned target. The volume of distribution, body weights and nonrenal clearance significantly contributed to drug dosing adaptation especially in the specific population. CONCLUSIONS: A meropenem regimen of 750 mg q 8 h was recommended for Asian critically illpatients receiving 2 different CRRT modalities with standard and high effluent rates. Clinical validation of these results is needed.
Authors: Ashley E Levack; Kathleen Turajane; Daniel A Driscoll; Xu Yang; Andy O Miller; Mathias P Bostrom; David S Wellman; Alberto V Carli Journal: J Orthop Res Date: 2021-07-12 Impact factor: 3.102