Authors (including presenting author) :
Kwan HS(1), Ho KY(1), Siu KL(2), Lam TN(3), Law KM(1), Ng TM(1), Chu MW(1), Leung YS(1)
Affiliation :
(1)Department of Pharmacy, Queen Elizabeth Hospital, Hong Kong
(2)Department of Paediatrics, Queen Elizabeth Hospital, Hong Kong
(3)School of Pharmacy, Faculty of Medicine, the Chinese University of Hong Kong
Introduction :
Despite good antibacterial activity against resistant gram-positive infections, clinical use of vancomycin is often complicated by its narrow therapeutic range and high pharmacokinetic variability. Significant challenges remain on achieving therapeutic targets with conventional dosing, like NeoFax®. A vancomycin population pharmacokinetic model was developed based on local clinical data to provide an individualized dosing recommendation. With aid of the model, it may be possible to shorten the time-to-reach target, increase the proportion of target attainment and reduce the number of blood sample collection. Physicians also have a choice to use area under the curve (AUC) guided dosing and monitoring for MRSA infections.
Objectives :
To evaluate the performance of a population pharmacokinetic model in neonates in providing an individualized dosing recommendation for optimal vancomycin activity.
Methodology :
A retrospective study was conducted in NICU of Queen Elizabeth Hospital (QEH) from 1 January to 31 December 2019. Performance of model-based dose was compared with actual prescribed dose in terms of the difference in proportion of therapeutic target attainment. Correlation of 24-hour AUC (AUC24h) and steady-state trough, as well as difference between pharmacokinetic parameter estimates with two-sample (peak and trough) approach and one-sample (trough only) approach were also analysed.
Result & Outcome :
The proportion of therapeutic target attainment with model-based dose (60%) is slightly higher than actual prescribed dose (51%), yet more clinical data may be required to show a significant difference (p = 0.290). A strong correlation was found between calculated AUC24h and measured trough (adjusted r = 0.960), and a trough level of 9.9 mg/L is required to achieve AUC24h ≥ 400 mg h/L. The estimation of pharmacokinetic parameters with a one-sample approach is also similar as compared to two-sample approach (adjusted r of elimination constant, Ke = 0.997; adjusted r of volume of distribution, Vd = 0.994).
Conclusion: The model-based dose showed a slightly higher proportion of therapeutic target attainment as compared to actual prescribed dose, yet more clinical data may be required to show significance. The model may assist pharmacists in providing vancomycin therapeutic drug monitoring (TDM) service in local NICUs by shortening the time-to-reach target and increasing the proportion of target attainment.
