Multiple intravenous doses of paracetamol result in a predictable pharmacokinetic profile in very preterm infants. (15th April 2014)

• Record Type: Journal Article
• Authors: van, C; Derijks, L; Anand, KJS; van, RA; Neef, C; Kramer, BW; Andriessen, P
• Is Part Of: Acta pædiatrica. Volume 103:Number 6(2014:Jun.)
• Page Start: 612
• Page End: 617
• Publication Date: 2014-04-15
• Subjects: Pediatrics -- Periodicals; Pediatrics; 618.92
• DOI: 10.1111/apa.12638
• Languages: English
• ISSNs: 0803-5253

Abstract

<abstract abstract-type="main" id="apa12638-abs-0001"> <title>Abstract</title> <sec id="apa12638-sec-0001" sec-type="section"> <title>Aim</title> <p>The therapeutic options available to treat neonatal pain are limited, and one alternative for nonopioid systemic treatment is paracetamol. However, pharmacokinetic data from prolonged administration of intravenous paracetamol in neonates are limited. The aim of this study was to present pharmacokinetics after multiple dose of intravenous paracetamol in very preterm infants of <32 weeks' gestation.</p> </sec> <sec id="apa12638-sec-0002" sec-type="section"> <title>Methods</title> <p>Fifteen very preterm infants received five, six‐hourly doses of intravenous paracetamol (7.5 mg/kg). Blood samples were taken to measure paracetamol, glutathione and hepatic function, together with urine samples for paracetamol metabolites.</p> </sec> <sec id="apa12638-sec-0003" sec-type="section"> <title>Results</title> <p>A two‐compartment pharmacokinetic model gave the best fit for all individual patients and resulted in a predictable pharmacokinetic profile. The estimated pharmacokinetic population parameters were volume of distribution 0.764 ± 0.225 L/kg, elimination rate constant (k<sub>e</sub>) 0.117 ± 0.091/h and intercompartment rate constants k<sub>12</sub> 0.607 ± 0.734/h and k<sub>21</sub> 1.105 ± 0.762/h.</p> </sec> <sec id="apa12638-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Our study found that multiple doses of intravenous paracetamol resulted in a predictable pharmacokinetic profile in very preterm infants. Increases in postmenstrual age and weight were associated with increased clearance. No evidence of hepatotoxicity was found.</p> </sec> </abstract>