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EFFECT OF PDA ON GENTAMICIN PHARMACOKINETICS IN BABIES < 1500 GRAMS

As part of a study of variables affecting gentamicin (G) pharmacokinetics in neonates, we examined the effect of patent ductus arteriosus (PDA) in babies <1500g. G levels were drawn at 1,4 and 8 hours. Data points were computer fitted into a one compartment, first order, open pharmacokinetic model by the method of least squares. The half life (T1/2), elimination rate constant(Ke), and distribution volume (Vd) were derived. We analyzed G pharmacokinetics in 8 babies without PDA (1161±258g) (mean±SD) and 9 babies with proven PDA (1000±255g). Six babies with PDA were treated (968±269g).T1/2 in patients without PDA (7.4±4.4hrs), with PDA (8.1±3.3 hrs), and with PDAs requiring treatment (9.4±1.7hrs) were not significantly different. Vd, however, was .422±.078L/kg in babies without PDA, .724±.367L/kg in babies with PDA (p=.02), and .839±.40L/kg in babies treated for PDA (p=.006). Three babies had G pharmacokinetics done before and after treatment. In each case, the Vd decreased substantially (from 1.41 to .42L/kg, 1.26 to .68L/kg, and .68 to .49L/kg).These results show that 1) babies <1500g with PDAs have larger Vds than those without PDAs, 2) babies whose PDAs require treatment have even higher Vds. In addition, Vd can drop substantially after treatment. We conclude 1) babies <1500g with PDAs may require higher G doses to achieve therapeutic peak levels, and 2) babies with PDAs who have therapeutic G levels should be reevaluated after therapy.