Pharmacokinetics of ticarcillin-clavulanate in premature infants.

British journal of clinical pharmacology 2019 May

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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. © 2019 The British Pharmacological Society.

Citation

Kevin M Watt, Christoph P Hornik, Stephen J Balevic, Gratias Mundakel, C Michael Cotten, Barrie Harper, Daniel K Benjamin, Ravinder Anand, Matthew Laughon, P Brian Smith, Michael Cohen-Wolkowiez, Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee. Pharmacokinetics of ticarcillin-clavulanate in premature infants. British journal of clinical pharmacology. 2019 May;85(5):1021-1027