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Drug Res (Stuttg) 2020; 70(10): 455-462
DOI: 10.1055/a-1233-3582
Original Article

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

Nasir Idkaidek 
1   College of Pharmacy, University of Petra, Amman, Jordan
,
Salim Hamadi
1   College of Pharmacy, University of Petra, Amman, Jordan
,
Rabab Bani-Domi
1   College of Pharmacy, University of Petra, Amman, Jordan
,
Ibrahim Al-Adham
1   College of Pharmacy, University of Petra, Amman, Jordan
,
Motasem Alsmadi 
2   College of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan
,
Faten Awaysheh
3   Royal Medical Services, Queen Rania Children Hospital, Amman, Jordan
,
Hisham Aqrabawi
3   Royal Medical Services, Queen Rania Children Hospital, Amman, Jordan
,
Ahmad Al-Ghazawi
4   Triumpharma LLC, Amman, Jordan
,
Ayman Rabayah
4   Triumpharma LLC, Amman, Jordan
› Author Affiliations Funding: This research was funded by Petra University fund # 4–2019.
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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.

Key words

antibacterial drugs, pharmacology, pharmaceutics, SECS - TDM - Gentamicin - Pk-Sim - PBPK - Preterm infants


Publication History

Received: 05 April 2020

Accepted: 01 August 2020

Article published online:
02 September 2020

© 2020. Thieme. All rights reserved.

© Georg Thieme Verlag KG
Stuttgart · New York

 

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