Multiple intravenous doses of paracetamol result in a predictable pharmacokinetic profile in very preterm infants

C. van Ganzewinkel, L. Derijks, K.J.S. Anand, R.A. van Lingen, C. Neef, B.W. Kramer, P. Andriessen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

AimThe 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 <32weeks' gestation. MethodsFifteen very preterm infants received five, six-hourly doses of intravenous paracetamol (7.5mg/kg). Blood samples were taken to measure paracetamol, glutathione and hepatic function, together with urine samples for paracetamol metabolites. ResultsA 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 0.7640.225L/kg, elimination rate constant (k(e)) 0.117 +/- 0.091/h and intercompartment rate constants k(12) 0.607 +/- 0.734/h and k(21) 1.105 +/- 0.762/h. ConclusionOur 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.
Original languageEnglish
Pages (from-to)612-617
JournalActa Paediatrica
Volume103
Issue number6
DOIs
Publication statusPublished - 1 Jan 2014

Cite this

van Ganzewinkel, C., Derijks, L., Anand, K. J. S., van Lingen, R. A., Neef, C., Kramer, B. W., & Andriessen, P. (2014). Multiple intravenous doses of paracetamol result in a predictable pharmacokinetic profile in very preterm infants. Acta Paediatrica, 103(6), 612-617. https://doi.org/10.1111/apa.12638
van Ganzewinkel, C. ; Derijks, L. ; Anand, K.J.S. ; van Lingen, R.A. ; Neef, C. ; Kramer, B.W. ; Andriessen, P. / Multiple intravenous doses of paracetamol result in a predictable pharmacokinetic profile in very preterm infants. In: Acta Paediatrica. 2014 ; Vol. 103, No. 6. pp. 612-617.
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title = "Multiple intravenous doses of paracetamol result in a predictable pharmacokinetic profile in very preterm infants",
abstract = "AimThe 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 <32weeks' gestation. MethodsFifteen very preterm infants received five, six-hourly doses of intravenous paracetamol (7.5mg/kg). Blood samples were taken to measure paracetamol, glutathione and hepatic function, together with urine samples for paracetamol metabolites. ResultsA 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 0.7640.225L/kg, elimination rate constant (k(e)) 0.117 +/- 0.091/h and intercompartment rate constants k(12) 0.607 +/- 0.734/h and k(21) 1.105 +/- 0.762/h. ConclusionOur 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.",
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van Ganzewinkel, C, Derijks, L, Anand, KJS, van Lingen, RA, Neef, C, Kramer, BW & Andriessen, P 2014, 'Multiple intravenous doses of paracetamol result in a predictable pharmacokinetic profile in very preterm infants', Acta Paediatrica, vol. 103, no. 6, pp. 612-617. https://doi.org/10.1111/apa.12638

Multiple intravenous doses of paracetamol result in a predictable pharmacokinetic profile in very preterm infants. / van Ganzewinkel, C.; Derijks, L.; Anand, K.J.S.; van Lingen, R.A.; Neef, C.; Kramer, B.W.; Andriessen, P.

In: Acta Paediatrica, Vol. 103, No. 6, 01.01.2014, p. 612-617.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Multiple intravenous doses of paracetamol result in a predictable pharmacokinetic profile in very preterm infants

AU - van Ganzewinkel, C.

AU - Derijks, L.

AU - Anand, K.J.S.

AU - van Lingen, R.A.

AU - Neef, C.

AU - Kramer, B.W.

AU - Andriessen, P.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - AimThe 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 <32weeks' gestation. MethodsFifteen very preterm infants received five, six-hourly doses of intravenous paracetamol (7.5mg/kg). Blood samples were taken to measure paracetamol, glutathione and hepatic function, together with urine samples for paracetamol metabolites. ResultsA 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 0.7640.225L/kg, elimination rate constant (k(e)) 0.117 +/- 0.091/h and intercompartment rate constants k(12) 0.607 +/- 0.734/h and k(21) 1.105 +/- 0.762/h. ConclusionOur 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.

AB - AimThe 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 <32weeks' gestation. MethodsFifteen very preterm infants received five, six-hourly doses of intravenous paracetamol (7.5mg/kg). Blood samples were taken to measure paracetamol, glutathione and hepatic function, together with urine samples for paracetamol metabolites. ResultsA 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 0.7640.225L/kg, elimination rate constant (k(e)) 0.117 +/- 0.091/h and intercompartment rate constants k(12) 0.607 +/- 0.734/h and k(21) 1.105 +/- 0.762/h. ConclusionOur 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.

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JO - Acta Paediatrica

JF - Acta Paediatrica

SN - 0803-5253

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ER -