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
