BackgroundGentamicin is commonly used in the NICU setting and is often administered via long lines, which increases variability in the rate of administration. We aimed to model drug delivery pharmacokinetic parameters for intravenous gentamicin administered via umbilical venous catheters (UVCs).MethodsData was modelled from infusion simulations of gentamicin delivery using UVCs with a background flow rate of 0.5 ml/h.1 Different combinations of dose (2 mg, 5 mg) were given by bolus injection over 3–5 minutes, followed by a normal saline flush (1 ml, 2 ml). Gentamicin levels were measured at 5 minute intervals over an hour via high pressure liquid chromatography.Phoenix Certara (version 8.1) was used for modelling. An extravascular model with clearance removed was used to predict parameters: absorption constant (Ka), time lag (Tlag), and bioavailability (F). F was used to enable an estimate of the variability in dose administered. Different error models were tested to ascertain which best described the data.ResultsAn extravascular one compartment model with first order absorption and additive error best described the data. Estimates for the model with a 2 mg dose and 1 ml flush were Ka 0.34L/min, Tlag 1.28min, F 0.97, standard deviation (stdev) 0.14. For 2 mg, 2 ml flush, estimates were Ka 0.86L/min, Tlag 3.01min, F 0.87, stdev 0.01. For 5 mg, 1 ml flush, estimates were Ka 0.48L/min, Tlag 3.13min, F 1.03, stdev 0.12. For 5 mg, 2 ml flush, estimates were Ka 0.83L/min, Tlag 3.29min, F 1.09, stdev 0.02. For each model epsshrinkage and nshrinkage for Tlag and F were low, however nshrinkage for ka was 0.9999.ConclusionThis is the first known modelling of gentamicin delivery kinetics. The studies all had high nshrinkage for Ka, therefore the individual estimates of ka may be unreliable. Further studies with a higher number of replicates would provide more favourable data for estimating Ka.ReferenceLala AC ( 2016). Variability in neonatal gentamicin administration influencing drug delivery kinetics (Thesis, Master of Medical Science). University of Otago.Disclosure(s)No conflict of interest declared. Funding for research via the Freemasons Society of New Zealand.
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