Saeed Alqahtani1, Manal Abouelkheir2, Abdullah Alsultan3,4, Yasmine Elsharawy5, Aljawharah Alkoraishi5, Reem Osman6, Wael Mansy3. 1. Department of Clinical Pharmacy, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh, 11451, Saudi Arabia. saeed@ksu.edu.sa. 2. Pediatric Clinical Pharmacy Services, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia. 3. Department of Clinical Pharmacy, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh, 11451, Saudi Arabia. 4. Clinical Pharmacokinetics and Pharmacodynamics Unit, King Saud University Medical City, Riyadh, Saudi Arabia. 5. Drug and Poison Information Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia. 6. Drug Information Center, Sultan Bin Abdulaziz Humanitarian City, King Saud University, Riyadh, Saudi Arabia.
Abstract
OBJECTIVE: Our objective was to determine the population pharmacokinetic parameters of amikacin in pediatric patients to contribute to the future development of a revised optimum dose and population-specific dosing regimens. METHODS: We performed a retrospective chart review in non-critical pediatric patients (aged 1-12 years) who received amikacin for suspected or proven Gram-negative infection at a university hospital. The population pharmacokinetic models were developed using Monolix 4.4. Pharmacokinetic/pharmacodynamic (PK/PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. RESULTS: The analysis included 134 amikacin plasma concentrations from 67 patients with a mean ± standard deviation age of 4.1 ± 3.9 years and bodyweight of 15 ± 8.4 kg. The patients received an amikacin total daily dose (TDD) of 23 ± 7.3 mg/kg, which resulted in peak and trough concentrations of 20.65 ± 7.6 and 2.4 ± 1.7 mg/l, respectively. The estimated pharmacokinetic parameters for amikacin were 1.2 l/h and 6.5 l for total body clearance (CL) and the volume of distribution (V), respectively. Dosing simulations showed that the standard dosing regimen (15 mg/kg/day) of amikacin achieved the PK/PD target of peak serum concentration (Cpeak)/minimum inhibitory concentration (MIC) ≥ 8 for an MIC of 2 mg/l; higher doses were required to achieve higher MIC values. CONCLUSION: The simulation results indicated that amikacin 20 mg/kg once daily provided a higher probability of target attainment with lower toxicity than dosing three times daily. In addition, combination therapy is recommended for pathogens with an MIC of ≥ 8 mg/l.
OBJECTIVE: Our objective was to determine the population pharmacokinetic parameters of amikacin in pediatric patients to contribute to the future development of a revised optimum dose and population-specific dosing regimens. METHODS: We performed a retrospective chart review in non-critical pediatric patients (aged 1-12 years) who received amikacin for suspected or proven Gram-negative infection at a university hospital. The population pharmacokinetic models were developed using Monolix 4.4. Pharmacokinetic/pharmacodynamic (PK/PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. RESULTS: The analysis included 134 amikacin plasma concentrations from 67 patients with a mean ± standard deviation age of 4.1 ± 3.9 years and bodyweight of 15 ± 8.4 kg. The patients received an amikacin total daily dose (TDD) of 23 ± 7.3 mg/kg, which resulted in peak and trough concentrations of 20.65 ± 7.6 and 2.4 ± 1.7 mg/l, respectively. The estimated pharmacokinetic parameters for amikacin were 1.2 l/h and 6.5 l for total body clearance (CL) and the volume of distribution (V), respectively. Dosing simulations showed that the standard dosing regimen (15 mg/kg/day) of amikacin achieved the PK/PD target of peak serum concentration (Cpeak)/minimum inhibitory concentration (MIC) ≥ 8 for an MIC of 2 mg/l; higher doses were required to achieve higher MIC values. CONCLUSION: The simulation results indicated that amikacin 20 mg/kg once daily provided a higher probability of target attainment with lower toxicity than dosing three times daily. In addition, combination therapy is recommended for pathogens with an MIC of ≥ 8 mg/l.
Authors: Despina G Contopoulos-Ioannidis; Nikos D Giotis; Dimitra V Baliatsa; John P A Ioannidis Journal: Pediatrics Date: 2004-07 Impact factor: 7.124
Authors: Andres Perez-Lopez; Sathyavathi Sundararaju; Hassan Al-Mana; Kin Ming Tsui; Mohammad Rubayet Hasan; Mohammed Suleiman; Mohammed Janahi; Eman Al Maslamani; Patrick Tang Journal: Front Microbiol Date: 2020-11-11 Impact factor: 5.640