Vancomycin Pharmacokinetics Throughout Life: Results from a Pooled Population Analysis and Evaluation of Current Dosing Recommendations
| Autor: | Nicolas Simon, Pieter Colin, Dolores Santos-Buelga, Karel Allegaert, Michael J. Dolton, Michel Struys, Alison H. Thomson, Daniel J. Touw, Jason A. Roberts, Fabio Silvio Taccone, Ana Martín-Suárez, Matthijs de Hoog, Emilia Barcia, Masato Yamamoto, Lo Yl, Douglas J. Eleveld, Eyob Adane |
|---|---|
| Přispěvatelé: | Pediatric Surgery, Pediatrics, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Biopharmaceuticals, Discovery, Design and Delivery (BDDD), Groningen Research Institute for Asthma and COPD (GRIAC), Pharmaceutical Analysis, Medicinal Chemistry and Bioanalysis (MCB), University Medical Center Groningen [Groningen] (UMCG), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Strathclyde [Glasgow], The University of Sydney, Erasmus University Rotterdam, University of Queensland [Brisbane], Ohio Northern University, Nagoya City University [Nagoya, Japan], Universidad de Salamanca, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université libre de Bruxelles (ULB), University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), HAL AMU, Administrateur, University of Malaya [Kuala Lumpur, Malaisie] |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Aging CLEARANCE INFECTIOUS-DISEASES SOCIETY CHILDREN Pharmacologie GUIDELINES 030226 pharmacology & pharmacy 0302 clinical medicine Blood serum Medicine and Health Sciences Pharmacology (medical) education.field_of_study medicine.diagnostic_test Middle Aged Anti-Bacterial Agents 3. Good health Area Under Curve Creatinine Practice Guidelines as Topic Vancomycin Female Drug Monitoring medicine.drug Adult RM medicine.medical_specialty CONTINUOUS-INFUSION 030106 microbiology Population Models Biological 03 medical and health sciences ADULT Pharmacokinetics Internal medicine medicine Humans AMERICA Dosing education Pharmacology business.industry Postmenstrual Age NONMEM MODEL [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie Therapeutic drug monitoring [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie business |
| Zdroj: | Clinical Pharmacokinetics, 58(6), 767-780. Adis Clinical Pharmacokinetics, 58(6), 767-780. Springer International Publishing AG Clinical Pharmacokinetics Clinical Pharmacokinetics, Springer Verlag, 2019, 58 (6), pp.767-780. ⟨10.1007/s40262-018-0727-5⟩ Clinical pharmacokinetics, 58 (6 CLINICAL PHARMACOKINETICS |
| ISSN: | 1179-1926 0312-5963 |
| Popis: | Background and Objectives: Uncertainty exists regarding the optimal dosing regimen for vancomycin in different patient populations, leading to a plethora of subgroup-specific pharmacokinetic models and derived dosing regimens. We aimed to investigate whether a single model for vancomycin could be developed based on a broad dataset covering the extremes of patient characteristics. Furthermore, as a benchmark for current dosing recommendations, we evaluated and optimised the expected vancomycin exposure throughout life and for specific patient subgroups. Methods: A pooled population-pharmacokinetic model was built in NONMEM based on data from 14 different studies in different patient populations. Steady-state exposure was simulated and compared across patient subgroups for two US Food and Drug Administration/European Medicines Agency-approved drug labels and optimised doses were derived. Results: The final model uses postmenstrual age, weight and serum creatinine as covariates. A 35-year-old, 70-kg patient with a serum creatinine level of 0.83 mg dL−1 (73.4 µmol L−1) has a V1, V2, CL and Q2 of 42.9 L, 41.7 L, 4.10 L h−1 and 3.22 L h−1. Clearance matures with age, reaching 50% of the maximal value (5.31 L h−1 70 kg−1) at 46.4 weeks postmenstrual age then declines with age to 50% at 61.6 years. Current dosing guidelines failed to achieve satisfactory steady-state exposure across patient subgroups. After optimisation, increased doses for the Food and Drug Administration label achieve consistent target attainment with minimal (± 20%) risk of under- and over-dosing across patient subgroups. Conclusions: A population model was developed that is useful for further development of age and kidney function-stratified dosing regimens of vancomycin and for individualisation of treatment through therapeutic drug monitoring and Bayesian forecasting. SCOPUS: ar.j info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink