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The steady state pharmacokinetics of trientine in Wilson disease patients

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

Abstract

Purpose

To determine the steady state pharmacokinetics of trientine in children (≥ 12 years of age) and adult patients who had been receiving trientine dihydrochloride therapy prior to the study.

Methods

Twenty patients were exposed to trientine (trientine dihydrochloride capsules supplied by Univar) after standard oral dosing as part of ongoing therapy. Plasma trientine concentration was determined pre-dose and at 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 h post-dose. Concentrations of trientine in plasma were determined by LC-MS/MS using a validated bioanalytical method with stable labelled trientine as the internal standard.

Results

Trientine was generally absorbed fairly rapidly with a median Tmax of 1.49 h (range, 0.48–4.08 h). There was some variability in exposure, with a 10-fold range in Cmax, and a 13.8-fold range in AUC0-t. This variability was slightly lower when PK parameters were dose-normalised (6.7-fold range in Cmax/D and an 11.6-fold range in AUC0-t/D). The terminal half-life, which could be defined in 14 of the 20 patients, was broadly consistent between patients (range of 2.33 to 6.99 h). There was no marked difference in pharmacokinetics between adult patients (n = 16) and children (n = 4). The Cmax range was 506 to 3100 ng/mL in adults and 309 to 1940 ng/mL in children—the equivalent ranges for AUC0-t were 1240 to 17,100 ng/mL h and 1500 to 8060 ng/mL h. When PK parameters were normalised for administered dose, the Cmax/D and AUC0-t/D for children were contained within the ranges for the adult patients.

Conclusions

The steady state pharmacokinetics of trientine in Wilson disease patients were broadly similar to that reported in healthy subjects.

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Acknowledgements

The authors wish to thank Johanna Braun, Christian Rupp, Daniel Gotthardt and Wolfgang Stremmel for their expertise and clinical contribution. The authors wish to acknowledge GfK for medical writing assistance.

Funding

This work was funded by Univar B.V. which had no influence on the results of the present study.

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Authors and Affiliations

  1. University Hospital Heidelberg, Heidelberg, Germany

    Jan Pfeiffenberger & Karl Heinz Weiss

  2. Univar B.V., Rotterdam, Netherlands

    Carlot Kruse

  3. ICON Consulting Services, Marlow, UK

    Peter Mutch & Andrew Harker

Authors
  1. Jan Pfeiffenberger
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  2. Carlot Kruse
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  3. Peter Mutch
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  4. Andrew Harker
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  5. Karl Heinz Weiss
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Contributions

JP designed and performed the study, discussed the results and contributed to the final manuscript.

CK discussed the results and contributed to the final manuscript.

PM analysed the samples, discussed the results and contributed to the final manuscript.

AH analysed the samples, discussed the results and contributed to the final manuscript.

KHW designed and performed the study, discussed the results and contributed to the final manuscript.

Corresponding author

Correspondence to Karl Heinz Weiss.

Ethics declarations

The Ethics Committee of the Medical Faculty Heidelberg approved the study protocol and use of trientine in these patients. Informed consent was obtained from all patients prior to receiving any pre-study assessments.

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Pfeiffenberger, J., Kruse, C., Mutch, P. et al. The steady state pharmacokinetics of trientine in Wilson disease patients. Eur J Clin Pharmacol 74, 731–736 (2018). https://doi.org/10.1007/s00228-018-2424-6

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  • DOI: https://doi.org/10.1007/s00228-018-2424-6

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