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

Corresponding Author

C van Ganzewinkel

Division of Neonatology, Department of Pediatrics, Máxima Medical Centre, Veldhoven, The Netherlands

Correspondence

Christ-jan van Ganzewinkel, Division of Neonatology, Department of Pediatrics, Máxima Medical Centre, De Run 4600, 5504 MB Veldhoven, The Netherlands.

Tel: +31 408889354 |

Fax: +31 408889340 |

Email: [email protected]

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L Derijks,

L Derijks

Department of Clinical Pharmacy, Máxima Medical Centre, Veldhoven, The Netherlands

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KJS Anand,

KJS Anand

University of Tennessee Health Science Center, Le Bonheur Children's Hospital, Memphis, TN, USA

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RA van Lingen,

RA van Lingen

Division of Neonatology, Princess Amalia Department of Pediatrics, Isala Clinics, Zwolle, The Netherlands

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C Neef,

C Neef

Department of Clinical Pharmacy & Toxicology, Maastricht University Medical Centre, CAPHRI School for Public Health and Primary Care, Maastricht, The Netherlands

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BW Kramer,

BW Kramer

Department of Pediatrics, Maastricht University Medical Centre, Maastricht, The Netherlands

School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands

School of Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands

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P Andriessen,

P Andriessen

Division of Neonatology, Department of Pediatrics, Máxima Medical Centre, Veldhoven, The Netherlands

Faculty of Health, Medicine and Life Science, Maastricht University, Maastricht, The Netherlands

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C van Ganzewinkel,

Corresponding Author

C van Ganzewinkel

Division of Neonatology, Department of Pediatrics, Máxima Medical Centre, Veldhoven, The Netherlands

Correspondence

Christ-jan van Ganzewinkel, Division of Neonatology, Department of Pediatrics, Máxima Medical Centre, De Run 4600, 5504 MB Veldhoven, The Netherlands.

Tel: +31 408889354 |

Fax: +31 408889340 |

Email: [email protected]

Search for more papers by this author

L Derijks,

L Derijks

Department of Clinical Pharmacy, Máxima Medical Centre, Veldhoven, The Netherlands

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KJS Anand,

KJS Anand

University of Tennessee Health Science Center, Le Bonheur Children's Hospital, Memphis, TN, USA

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RA van Lingen,

RA van Lingen

Division of Neonatology, Princess Amalia Department of Pediatrics, Isala Clinics, Zwolle, The Netherlands

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C Neef,

C Neef

Department of Clinical Pharmacy & Toxicology, Maastricht University Medical Centre, CAPHRI School for Public Health and Primary Care, Maastricht, The Netherlands

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BW Kramer,

BW Kramer

Department of Pediatrics, Maastricht University Medical Centre, Maastricht, The Netherlands

School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands

School of Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands

Search for more papers by this author

P Andriessen,

P Andriessen

Division of Neonatology, Department of Pediatrics, Máxima Medical Centre, Veldhoven, The Netherlands

Faculty of Health, Medicine and Life Science, Maastricht University, Maastricht, The Netherlands

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First published: 21 March 2014

https://doi.org/10.1111/apa.12638

Citations: 18

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Abstract

Aim

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.

Methods

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.

Results

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_e) 0.117 ± 0.091/h and intercompartment rate constants k₁₂ 0.607 ± 0.734/h and k₂₁ 1.105 ± 0.762/h.

Conclusion

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.

References

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Volume103, Issue6

June 2014

Pages 612-617

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

Abstract

Aim

Methods

Results

Conclusion

References

Citing Literature

References

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

Abstract

Aim

Methods

Results

Conclusion

References

Citing Literature

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