1. Saliva versus Plasma Therapeutic Drug Monitoring of Gentamicin in Jordanian Preterm Infants. Development of a Physiologically-Based Pharmacokinetic (PBPK) Model and Validation of Class II Drugs of Salivary Excretion Classification System.
- Author
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Idkaidek N, Hamadi S, Bani-Domi R, Al-Adham I, Alsmadi M, Awaysheh F, Aqrabawi H, Al-Ghazawi A, and Rabayah A
- Subjects
- Bacterial Infections blood, Chromatography, High Pressure Liquid instrumentation, Chromatography, High Pressure Liquid methods, Dose-Response Relationship, Drug, Drug Dosage Calculations, Drug Monitoring instrumentation, Female, Gentamicins administration & dosage, Gentamicins adverse effects, Gentamicins isolation & purification, Humans, Infant, Low Birth Weight, Infant, Newborn, Infant, Premature, Jordan, Limit of Detection, Male, Ototoxicity blood, Ototoxicity etiology, Plasma chemistry, Saliva chemistry, Salivary Elimination physiology, Tandem Mass Spectrometry instrumentation, Tandem Mass Spectrometry methods, Bacterial Infections drug therapy, Drug Monitoring methods, Gentamicins pharmacokinetics, Models, Biological, Ototoxicity prevention & control
- Abstract
Gentamicin has proven to be a very successful treatment for bacterial infection, but it also can cause adverse effects, especially ototoxicity, which is irreversible. Therapeutic drug monitoring (TDM) in saliva is a more convenient non-invasive alternative compared to plasma. A physiologically-based pharmacokinetic (PBPK) model of gentamicin was built and validated using previously-published plasma and saliva data. The validated model was then used to predict experimentally-observed plasma and saliva gentamicin TDM data in Jordanian pediatric preterm infant patients measured using sensitive LCMS/MS method. A correlation was established between plasma and saliva exposures. The developed PBPK model predicted previously reported gentamicin levels in plasma, saliva and those observed in the current study. A good correlation was found between plasma and saliva exposures. The PBPK model predicted that gentamicin in saliva is 5-7 times that in plasma, which is in agreement with observed results. Saliva can be used as an alternative for TDM of gentamicin in preterm infant patients. Exposure to gentamicin in plasma and saliva can reliably be predicted using the developed PBPK model in patients., Competing Interests: The authors declare no conflict of interest., (Thieme. All rights reserved.)
- Published
- 2020
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