Pharmacokinetics of ticarcillin-clavulanate in premature infants

Feb-19

Journal Article

Authors:

Volume:
85

Pagination:
1021-1027

Issue:
5

Journal:
Br J Clin Pharmacol

PMID:
30710387

URL:
https://www.ncbi.nlm.nih.gov/pubmed/30710387

DOI:
10.1111/bcp.13882

Keywords:
Clavulanic Acids/administration & dosage/pharmacokinetics Computer Simulation Dose-Response Relationship, Drug Drug Dosage Calculations Female Humans Infant, Extremely Premature Infant, Newborn Male Microbial Sensitivity Tests Models, Biological Prospective Studies Staphylococcal Infections/*drug therapy/microbiology Staphylococcus/*drug effects/physiology Ticarcillin/administration & dosage/pharmacokinetics beta-Lactamase Inhibitors/administration & dosage/*pharmacokinetics clavulanate infants pharmacokinetics premature ticarcillin

Abstract:
<p>Ticarcillin-clavulanate covers a broad spectrum of pathogens that are common in premature infants. In infants &lt;30 weeks gestational age, pharmacokinetic data to guide ticarcillin-clavulanate dosing are lacking. We enrolled 15 premature infants &lt;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 &lt;14 days (0.050 L/kg/h [range 0.043-0.075]) compared with a PNA &gt;/=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 &lt;14 days) or q8h (PNA &gt;/= 14-45 days) achieved the target exposure for organisms with a minimum inhibitory concentration &lt;/=16 mu/mL in &gt;90% of simulated infants. For highly resistant organisms (minimum inhibitory concentration 32 mug/mL), increased dosing frequency or extended infusion are necessary.</p>