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Different pharmacokinetics of tramadol in mothers treated for labour pain and in their neonates

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

The aim of the present study was to investigate the pharmacokinetic profile of tramadol hydrochloride in neonates, born from mothers who underwent analgesia with tramadol for the relief of labour pain.

Methods

Intramuscular tramadol (100–250 mg) was administered to 22 mothers giving birth who requested pain relief. At the time of birth (1.5–6.0 h after last tramadol dose), maternal and umbilical blood samples were taken. Another venous blood sample was drawn from each neonate, and at the same time from its mother, at 1, 2, 3, 6 or 12 h post-partum, providing the data for a population pharmacokinetic evaluation of tramadol and its metabolite M1. Routine APGAR scores and a standard neurological and adaptive capacity test were considered for evaluation of the effect of tramadol on the neonates.

Results

Serum tramadol concentrations at the time of birth (t0) were 243±102 ng/ml (mean±SD, umbilical vein), 258±103 ng/ml (umbilical artery) and 250±113 ng/ml (maternal vein). Serum M1 concentrations were 52±27 ng/ml (umbilical vein), 47±24 ng/ml (umbilical artery) and 56±21 ng/ml (maternal vein). The two-compartment type elimination profiles during the first 12 h post-partum for neonates (and mothers, respectively) were characterised by terminal t1/2 (tramadol)=7.0 (7.2) h and t1/2 (metabolite M1)=85.0 (5.5) h.

Conclusion

The intramuscular application of tramadol in birth-giving mothers almost freely reaches the neonate, confirming a high degree of placental permeability. The neonates already possess the complete hepatic capacity for the metabolism of tramadol into its active metabolite. However, the renal elimination of the active tramadol metabolite M1 is delayed, in line with the slow maturation process of renal function in neonates. Despite this difference in pharmacokinetics between neonates and adults, the intramuscular application of tramadol at the recommended dosage range during delivery appears to effective in the relief of labour pain.

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Acknowledgements

The authors are thankful to the mothers and neonates who participated in the study at the Nijmegen Hospitals. The study was sponsored by the Medical Department of Grünenthal GmbH, Aachen, Germany, and by ALTANA Pharma bv, Zwanenburg, the Netherlands. CobraMed AG—Institut für Klinische Arzneimittelstudien, Kerpen, Germany, performed the evaluation of the study. The authors declare that the experiments are compliant with the current laws of the country in which the experiment was performed.

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Authors and Affiliations

  1. Department of Neonatology, University Medical Centre Sint Radboud, Postbus 9101, 6500, HB, Nijmegen, The Netherlands

    H. L. Claahsen-van der Grinten, I. Verbruggen & L. A. A. Kollée

  2. Department of Gynecology, University Medical Centre Sint Radboud, Postbus 9101, 6500, HB, Nijmegen, The Netherlands

    P. P. van den Berg

  3. Department of Gynecology, Canisius-Wilhelmina Hospital Nijmegen, Postbus 9015, 6500, GS, Nijmegen, The Netherlands

    J. M. J. Sporken

Authors
  1. H. L. Claahsen-van der Grinten
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  2. I. Verbruggen
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  3. P. P. van den Berg
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  4. J. M. J. Sporken
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  5. L. A. A. Kollée
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Correspondence to L. A. A. Kollée.

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Claahsen-van der Grinten, H.L., Verbruggen, I., van den Berg, P.P. et al. Different pharmacokinetics of tramadol in mothers treated for labour pain and in their neonates. Eur J Clin Pharmacol 61, 523–529 (2005). https://doi.org/10.1007/s00228-005-0955-0

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  • DOI: https://doi.org/10.1007/s00228-005-0955-0

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