Abstract
We examined half time (Pt 1/2) and distribution volume (Vd) of V in 22 (16 preterm and 6 term) critically ill neonates. V was dosed: 20 mg/kg/d OD (<800g), 30 mg/kg/d OD (800-1200g), 40 mg/kg/d TID (> 1200g), as 60 min infusion. Target concentrations were 20-40 mcg/ml (pk) and <10 mcg/ml (tr). 88 drug levels were drawn: peak (pk) level 60 min after end of infusion, trough (tr) level prior to the next dose. V concentrations were measured by fluorescence polarisation immunoassay (TDX Abbott). Data are m ± sD:Results: Pt 1/2 is decreasing with PCA, but Vd is not related to PCA in our population. 36% (16/44) of pk levels were not within the therapeutic range: 2 below, 14 above the range. 30% (13/44) of tr levels were above the therapeutic range. In 64% (28/44) the dosing schedule was changed according to pharmacokinetic data: increased dose (7), decreased dose (15), lengthened interval (12), shortened interval (3). The adjusted average dosage in our population was: for PCA < 30 wks: 17 mg/kg every 25 h; PCA 30-37 wks: 17 mg/kg every 20 h; PCA > 37 wks: 18 mg/kg every 19 h.Conclusion: Therapeutic drug monitoring of V is essential because of high interpatient variability, to avoid toxicity and to ensure therapeutic blood levels. We suggest a revision of current dosing recommendations in preterm neonates.
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