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Burckhardt BB, Tins J, Ramusovic S, et al. Tailored Assays for Pharmacokinetic and Pharmacodynamic Investigations of Aliskiren and Enalapril in Children: An Application in Serum, Urine, and Saliva. J Pediatr Pharmacol Ther. 2015;20(6):431-52doi: 10.5863/1551-6776-20.6.431.
Burckhardt, B. B., Tins, J., Ramusovic, S., & Läer, S. (2015). Tailored Assays for Pharmacokinetic and Pharmacodynamic Investigations of Aliskiren and Enalapril in Children: An Application in Serum, Urine, and Saliva. The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG, 20(6), 431-52. https://doi.org/10.5863/1551-6776-20.6.431
Burckhardt, Bjoern B, et al. "Tailored Assays for Pharmacokinetic and Pharmacodynamic Investigations of Aliskiren and Enalapril in Children: An Application in Serum, Urine, and Saliva." The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG vol. 20,6 (2015): 431-52. doi: https://doi.org/10.5863/1551-6776-20.6.431
Burckhardt BB, Tins J, Ramusovic S, Läer S. Tailored Assays for Pharmacokinetic and Pharmacodynamic Investigations of Aliskiren and Enalapril in Children: An Application in Serum, Urine, and Saliva. J Pediatr Pharmacol Ther. 2015 Nov-Dec;20(6):431-52. doi: 10.5863/1551-6776-20.6.431. PMID: 26766933; PMCID: PMC4708953.
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J Pediatr Pharmacol Ther. 2015 Nov-Dec;20(6):431-52. doi: 10.5863/1551-6776-20.6.431.

Tailored Assays for Pharmacokinetic and Pharmacodynamic Investigations of Aliskiren and Enalapril in Children: An Application in Serum, Urine, and Saliva.

The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG

Bjoern B Burckhardt, Jutta Tins, Sergej Ramusovic, Stephanie Läer

Affiliations

  1. Department of Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine-University, Düsseldorf, Germany.

PMID: 26766933 PMCID: PMC4708953 DOI: 10.5863/1551-6776-20.6.431

Abstract

OBJECTIVES: Drugs that are effectively used to treat hypertension in adults (e.g., enalapril) have not been sufficiently investigated in children. Studies required for pediatric approval require special consideration regarding ethics, study design, and conduct and are also associated with special demands for the bioanalytic method. Pediatric-appropriate assays can overcome these burdens and enable systematic investigations of pharmacokinetics and pharmacodynamic in all pediatric age groups.

METHODS: Tailored assays were developed for pharmacokinetic investigation of a drug in 100 μL of serum, saliva, and urine. All assays were applied in a proof-of-concept study to 22 healthy volunteers who had been given 300 mg aliskiren hemifumarate or 20 mg enalapril maleate and allowed for dense sampling. Changes in humoral parameters of the renin-angiotensin-aldosterone system were also evaluated with 6 parameters in 2.1 mL blood per time point.

RESULTS: The pharmacokinetic results of aliskiren and enalapril obtained by low-volume assays in serum and urine were comparable to that noted in the literature. The dense sampling enabled very detailed concentration-time profiles that showed high intersubject variability and biphasic absorption behavior of aliskiren. The replacement of invasive sampling by saliva collection appears inappropriate for both drugs because the correlations of drug concentrations in both fluids were low. A low-volume assay was also used to determine values for in the renin-angiotensin-aldosterone system and to compare those results with the published literature.

CONCLUSION: These results support both the use of low-volume assays in pediatric research and the systematic investigation of their use in neonates and infants. Use of this assay methodology will increase information about drug pharmacokinetics and pharmacodynamics in this vulnerable population and might contribute to safe and effective use of pharmacotherapy.

Keywords: aliskiren; child; enalapril; enalaprilat; pharmacokinetics; renin-angiotensin system; saliva

References

  1. Rapid Commun Mass Spectrom. 2003;17(11):1157-62 - PubMed
  2. Clin Pharmacokinet. 2007;46(8):661-75 - PubMed
  3. Ann Allergy Asthma Immunol. 2015 Jan;114(1):63-4 - PubMed
  4. Clin Pharmacol Ther. 1994 Aug;56(2):160-8 - PubMed
  5. J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Oct 15;878(28):2685-92 - PubMed
  6. Acta Paediatr. 2011 Sep;100(9):1272-5 - PubMed
  7. J Clin Pharmacol. 2001 Oct;41(10):1064-74 - PubMed
  8. J Pharmacol Exp Ther. 1990 Apr;253(1):362-8 - PubMed
  9. J Pediatr. 1989 Apr;114(4 Pt 1):650-4 - PubMed
  10. J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Dec 25;813(1-2):337-42 - PubMed
  11. Biomed Chromatogr. 2014 Dec;28(12):1679-91 - PubMed
  12. Eur J Clin Pharmacol. 2011 Dec;67(12):1263-71 - PubMed
  13. Br J Clin Pharmacol. 1982 Sep;14(3):357-62 - PubMed
  14. Ther Drug Monit. 2009 Dec;31(6):710-6 - PubMed
  15. Biopharm Drug Dispos. 2003 Oct;24(7):315-20 - PubMed
  16. Drug Metab Dispos. 2007 Aug;35(8):1418-28 - PubMed
  17. Hypertension. 2002 Jan;39(1):E1-8 - PubMed
  18. Clin Pediatr (Phila). 2013 Jul;52(7):599-607 - PubMed
  19. Can J Cardiol. 2013 Dec;29(12):1535-52 - PubMed
  20. Pediatr Crit Care Med. 2015 May;16(4):e101-6 - PubMed
  21. Anal Bioanal Chem. 2005 May;382(1):216-22 - PubMed
  22. J Pharm Biomed Anal. 2014 Aug 5;96:118-26 - PubMed
  23. Biopharm Drug Dispos. 2000 Dec;21(9):339-44 - PubMed
  24. Br J Clin Pharmacol. 1981 May;11(5):461-7 - PubMed
  25. Biomed Chromatogr. 2013 Apr;27(4):477-86 - PubMed
  26. Arch Dis Child. 1981 Apr;56(4):298-302 - PubMed
  27. Biopharm Drug Dispos. 1984 Jul-Sep;5(3):273-80 - PubMed
  28. Clin Pharmacokinet. 2008;47(8):515-31 - PubMed
  29. Biomed Chromatogr. 2012 Jun;26(6):697-702 - PubMed
  30. Int J Clin Pract. 2007 Sep;61(9):1461-8 - PubMed
  31. Psychoneuroendocrinology. 2004 Sep;29(8):1028-36 - PubMed
  32. J Clin Pathol. 1975 Aug;28(8):625-30 - PubMed
  33. Epilepsia. 2013 Jan;54(1):81-8 - PubMed
  34. J Pharm Biomed Anal. 2009 Jan 15;49(1):163-7 - PubMed
  35. J Hypertens. 2009 Sep;27(9):1719-42 - PubMed
  36. Pediatr Res. 2005 Dec;58(6):1233-7 - PubMed
  37. Int J Clin Pharm. 2013 Feb;35(1):30-6 - PubMed
  38. Drug Test Anal. 2012 Feb;4(2):94-103 - PubMed
  39. Br J Clin Pharmacol. 1986 Jan;21(1):63-9 - PubMed
  40. Biochem Biophys Res Commun. 2003 Sep 5;308(4):698-705 - PubMed
  41. Circulation. 1995 Jan 15;91(2):330-8 - PubMed

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