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.
Drug Res (Stuttg)
; 70(10): 455-462, 2020 Oct.
Article
in En
| MEDLINE
| ID: mdl-32877949
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bacterial Infections
/
Gentamicins
/
Drug Monitoring
/
Ototoxicity
/
Models, Biological
Type of study:
Etiology_studies
/
Prognostic_studies
Limits:
Female
/
Humans
/
Male
/
Newborn
Country/Region as subject:
Asia
Language:
En
Journal:
Drug Res (Stuttg)
Year:
2020
Document type:
Article
Affiliation country:
Jordan
Publication country:
ALEMANHA
/
ALEMANIA
/
DE
/
DEUSTCHLAND
/
GERMANY