ArticleClinical pharmacokinetics2022
Prediction of Tissue Exposures of Meropenem, Colistin, and Sulbactam in Pediatrics Using Physiologically Based Pharmacokinetic Modeling.
Article in Clinical pharmacokinetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Polymyxin B Intravenous Administration Strategy Guided by Minimum Inhibitory Concentration in Critically Ill Patients With Pulmonary Infection: Insights From PBPK Modeling.CPT: pharmacometrics & systems pharmacology · 2026Article
- Optimization of pediatric dosing regimens for aztreonam and amoxicillin/clavulanate combination therapy against multidrug-resistant bacteria.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Article
- A Physiologically Based Pharmacokinetic Model for the Prediction of Plasma and Bone Tissue Exposure after Prophylactic Administration of Ampicillin/Sulbactam in Patients with Osteonecrosis of the Jaw.Clinical pharmacokinetics · 2025Article
- Prediction of CYP3A4-mediated drug-drug interactions of a novel Bcl-2 inhibitor TQB3909 using physiologically based pharmacokinetic modeling.Cancer chemotherapy and pharmacology · 2025Article
- Drug-resistant gram-negative bacterial infections in children in the Oceania region: review of the epidemiology, antimicrobial availability, treatment, clinical trial and pharmacokinetic data, and key evidence gaps.The Lancet regional health. Western Pacific · 2025Review
- Physiologically Based Pharmacokinetic Modeling of Antibiotics in Children: Perspectives on Model-Informed Precision Dosing.Antibiotics (Basel, Switzerland) · 2025Review
- Personalized Dosing of Medicines for Children: A Primer on Pediatric Pharmacometrics for Clinicians.Paediatric drugs · 2024Review
- Utility and impact of quantitative pharmacology on dose selection and clinical development of immuno-oncology therapy.Cancer chemotherapy and pharmacology · 2024Review
- Prediction of tissue exposures of polymyxin-B, amikacin and sulbactam using physiologically-based pharmacokinetic modeling.Frontiers in microbiology · 2024Article
- Metabolomics revealed mechanism for the synergistic effect of sulbactam, polymyxin-B and amikacin combination againstFrontiers in microbiology · 2023Article
- Predicting the correct dose in children: Role of computational Pediatric Physiological-based pharmacokinetics modeling tools.CPT: pharmacometrics & systems pharmacology · 2023Review
- The combination effect of meropenem/sulbactam/polymyxin-B on the pharmacodynamic parameters for mutant selection windows against carbapenem-resistantFrontiers in microbiology · 2022Article
- Metabolomic profiling of polymyxin-B in combination with meropenem and sulbactam against multi-drug resistantFrontiers in microbiology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe combination of polymyxins, meropenem, and sulbactam demonstrated efficacy against multi-drug-resistant bacillus Acinetobacter baumannii. These three antibiotics are commonly used against major blood, skin, lung, and heart muscle infections.
objectiveThe objective of this study was to predict drug disposition and extrapolate the efficacy in these tissues using a physiologically based pharmacokinetic modeling approach that linked drug exposures to their target pharmacodynamic indices associated with antimicrobial activities against A. baumannii.
methodsAn adult physiologically based pharmacokinetic model was developed for meropenem, colistin, and sulbactam and scaled to pediatrics accounting for both renal and non-renal clearances. The model reliability was evaluated by comparing simulated plasma and tissue drug exposures to observed data. Target pharmacodynamic indices were used to evaluate whether pediatric and adult dosing regimens provided sufficient coverage.
resultsThe modeled plasma drug exposures in adults and pediatric patients were consistent with reported literature data. The mean fold errors for meropenem, colistin, and sulbactam were in the range of 0.710-1.37, 0.981-1.47, and 0.647-1.39, respectively. Simulated exposures in the blood, skin, lung, and heart were consistent with reported penetration rates. In a virtual pediatric population aged from 2 to < 18 years, the interpretive breakpoints were achieved in 85-90% of subjects for their targeted pharmacodynamic indices after administration of pediatric dosing regimens consisting of 30 mg/kg of meropenem, and 40 mg/kg of sulbactam three times daily as a 3-h or continuous infusion and 5 mg/kg/day of colistin base activity.
conclusionsThe physiologically based pharmacokinetic modeling supports pediatric dosing regimens of meropenem/colistin/sulbactam in a co-administration setting against infections in the blood, lung, skin, and heart tissues due to A. baumannii.
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