Yong Kyun Kim1, Dong-Hwan Lee2, Jaehyun Jeon3, Hang-Jea Jang4, Hyeon-Kuk Kim4, Kyubok Jin5, Sung-Nam Lim6, Sung Sook Lee6, Bong Soo Park7, Yang Wook Kim7, Jae-Gook Shin8, Sungmin Kiem9. 1. Division of Infectious Diseases, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea. 2. Hallym Institute for Clinical Medicine, Hallym University Medical Center, Anyang, Republic of Korea. 3. Department of Infectious Diseases, Division of Intensive Care Medicine, Sheikh Khalifa Specialty Hospital, North Ras Al Khaimah, United Arab Emirates. 4. Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea. 5. Division of Nephrology, Keimyung University Dongsan Medical Center, Daegu, Republic of Korea. 6. Division of Hemato-Oncology, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea. 7. Division of Nephrology, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea. 8. Department of Clinical Pharmacology, Inje University College of Medicine, Busan, Republic of Korea. 9. Division of Infectious Diseases, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea. Electronic address: smkimkor@paik.ac.kr.
Abstract
PURPOSE: The aim of this study was to investigate the population pharmacokinetic (PK) profile of meropenem in Korean patients with acute infections. METHODS: The study included 37 patients with a creatinine clearance ≤50 or >50 mL/min who received a 500- or 1000-mg dose of meropenem, respectively, infused intravenously over 1 hour every 8 hours. Blood samples were collected before and at 1, 1.5, and 5 hours after the start of the fourth infusion. The population PK analysis was conducted by using nonlinear mixed effect modeling software (NONMEM). Monte-Carlo simulations were performed to identify optimal dosing regimens. FINDINGS: Thirty-seven subjects completed the study. Meropenem PK variables were well described by using a one-compartment model. The typical values (relative SE) for weight-normalized clearance (CL) and Vd were 0.266 L/h/kg (12.29%) and 0.489 L/kg (11.01%), respectively. Meropenem CL was significantly influenced by the serum creatinine level, which explained 11% of the interindividual CK variability. The proposed equation to estimate meropenem CL in Korean patients was as follows: CL (L/h) = 0.266 × weight × [serum creatinine/0.74]-1.017. The simulation results indicate that the current meropenem dosing regimen may be suboptimal in patients infected with normal or augmented renal function. IMPLICATIONS: Prolonged infusions of meropenem over at least 2 hours should be considered, especially in patients with augmented renal function and those infected with pathogens for which the minimum inhibitory meropenem concentration is >1 μg/mL. Our results suggest an individualized meropenem dosing regimen for patients with abnormal renal function and those infected with pathogens with decreased in vitro susceptibility.
PURPOSE: The aim of this study was to investigate the population pharmacokinetic (PK) profile of meropenem in Korean patients with acute infections. METHODS: The study included 37 patients with a creatinine clearance ≤50 or >50 mL/min who received a 500- or 1000-mg dose of meropenem, respectively, infused intravenously over 1 hour every 8 hours. Blood samples were collected before and at 1, 1.5, and 5 hours after the start of the fourth infusion. The population PK analysis was conducted by using nonlinear mixed effect modeling software (NONMEM). Monte-Carlo simulations were performed to identify optimal dosing regimens. FINDINGS: Thirty-seven subjects completed the study. Meropenem PK variables were well described by using a one-compartment model. The typical values (relative SE) for weight-normalized clearance (CL) and Vd were 0.266 L/h/kg (12.29%) and 0.489 L/kg (11.01%), respectively. Meropenem CL was significantly influenced by the serum creatinine level, which explained 11% of the interindividual CK variability. The proposed equation to estimate meropenem CL in Korean patients was as follows: CL (L/h) = 0.266 × weight × [serum creatinine/0.74]-1.017. The simulation results indicate that the current meropenem dosing regimen may be suboptimal in patients infected with normal or augmented renal function. IMPLICATIONS: Prolonged infusions of meropenem over at least 2 hours should be considered, especially in patients with augmented renal function and those infected with pathogens for which the minimum inhibitory meropenem concentration is >1 μg/mL. Our results suggest an individualized meropenem dosing regimen for patients with abnormal renal function and those infected with pathogens with decreased in vitro susceptibility.