Pharmacokinetics of ticarcillin-clavulanate in premature infants

Abstract

Ticarcillin-clavulanate covers a broad spectrum of pathogens that are common in premature infants. In infants <30 weeks gestational age, pharmacokinetic data to guide ticarcillin-clavulanate dosing are lacking. We enrolled 15 premature infants <30 weeks gestational age, determined pharmacokinetic parameters, and performed dosing simulations to determine optimal dosing for ticarcillin-clavulanate. The infants had a median (range) postnatal age (PNA) of 18 days (6-44 days) and gestational age of 25 weeks (23-28 weeks). Clearance was lower in infants with a PNA <14 days (0.050 L/kg/h [range 0.043-0.075]) compared with a PNA ≥14-45 days (0.078 L/kg/h [0.047-0.100]), consistent with maturation of renal function. Dosing simulations determined that ticarcillin 75 mg/kg q12h (PNA <14 days) or q8h (PNA ≥ 14-45 days) achieved the target exposure for organisms with a minimum inhibitory concentration ≤16 μ/mL in >90% of simulated infants. For highly resistant organisms (minimum inhibitory concentration 32 μg/mL), increased dosing frequency or extended infusion are necessary.

Keywords: clavulanate; infants; pharmacokinetics; premature; ticarcillin.

© 2019 The British Pharmacological Society.

Figures

Figure 1

Target attainment rates for different ticarcillin dosing regimens for fraction of time the concentration of unbound drug remains above the minimum inhibitory concentration of 75%. Target attainment rate refers to the % of simulated infants who maintained an unbound ticarcillin concentration above the minimum inhibitory concentration for 75% of the dosing interval. The red horizontal line refers to a target attainment rate of 90%