Clinical Pharmacokinetics

, Volume 15, Issue 4, pp 245–253 | Cite as

The Influence of Renal Function on Clinical Pharmacokinetics of Moxonidine

  • W. Kirch
  • H. J. Hutt
  • V. Plänitz
Original Research Article

Summary

Investigations were carried out on 24 hypertensive or borderline hypertensive patients with different degrees of renal function. Eight had normal renal function [glomerular filtration rate (GFR) > 90 ml/min], 8 moderate (GFR 30 to 60 ml/min) and 8 severe renal impairment (GFR < 30 ml/min). All patients were given moxonidine 0.3mg once daily for 7 days and both pharmacokinetic and pharmacodynamic data were determined.

During moxonidine treatment plasma elimination half-life, area under the plasma concentration-time curve (AUC) and apparent total clearance (CLT) showed statistically significant differences among patients in the 3 groups. Elimination half-life was 2.6 ± 0.9 hours in patients with a GFR > 90 ml/min and increased to 6.9 ± 3.7 hours in those with a GFR < 30 ml/min (mean ± SD; p = 0.012). Correspondingly, AUC0–24h rose from 5.4 ± 2.7 to 17.2 ± 7.9 µg/L · h (p = 0.001), and CLT decreased from 1150 ± 602.1 ml/min to 369 ± 227.6 ml/min (p = 0.001).

These data suggest that once-daily administration of 0.3mg moxonidine may be appropriate in patients with impaired renal function. Independent of renal function, moxonidine was well tolerated in 22 of 24 patients. No deterioration in renal function as a consequence of the use of moxonidine was found. Thus, in patients with renal failure, dosage of moxonidine should be individually titrated according to the desired clinical response, as is recommended for hypertensive patients without renal impairment.

References

  1. Armah IB, Stenzel W. BE-5895, a new clonidine-type antihypertensive amino-pyrimidine derivative. Naunyn Schmiedeberg’s Archives of Pharmacology 316: R42, 1981CrossRefGoogle Scholar
  2. Bernstein KN, O’Connor DT. Antiadrenergic antihypertensive drugs: their effect on renal function. Annual Review of Pharmacology and Toxicology 24: 105–120, 1984PubMedCrossRefGoogle Scholar
  3. Cruickshank JM. The clinical importance of cardioselectivity and lipophilicity in β-blockers. American Heart Journal 100: 160–169, 1980PubMedCrossRefGoogle Scholar
  4. Gugler R. Pharmacokinetische Unterschiede zwischen β-Rezeptorenblockern. In Bolte & Schrey (Eds) Beta-Rezeptoren-blocker, pp. 19–22, Springer-Verlag, Berlin, Heidelberg, New York, 1981CrossRefGoogle Scholar
  5. Itskovitz HD. Clonidine and the kidney. Journal of Cardiovascular Pharmacology 2: 547–560, 1980CrossRefGoogle Scholar
  6. Kirch W, Köhler H, Braun W, von Gizycki C. The influence of renal function on plasma concentration, urinary excretion and antihypertensive effect of guanfacine. Clinical Pharmacokinetics 5: 476–483, 1980PubMedCrossRefGoogle Scholar
  7. Massarella JK, Khoo KCH, Szuna AJ, Sandor DA, Morganroth J, Aogaichi K. Pharmacokinetics of cibenzoline after single and repetitive dosing in healthy volunteers. Journal of Clinical Pharmacology 26: 125–130, 1986PubMedGoogle Scholar
  8. McAinsh J. Clinical pharmacokinetics of atenolol. Postgraduate Medical Journal 53: 74–78, 1977PubMedGoogle Scholar
  9. Morgan T. The use of centrally acting antihypertensive drugs in patients with renal disease. Chest 83 (Suppl. 2): 383–385, 1983PubMedGoogle Scholar
  10. Plänitz V. Crossover comparison of moxonidine and clonidine in mild to moderate hypertension. European Journal of Clinical Pharmacology 27: 147–152, 1984PubMedCrossRefGoogle Scholar
  11. Plänitz V. Intraindividual comparison of moxonidine and prazosin in hypertensive patients. European Journal of Clinical Pharmacology 29: 645–650, 1986PubMedCrossRefGoogle Scholar
  12. Plänitz V. Comparison of moxonidine and clonidine-HCI in treating patients with hypertension. Journal of Clinical Pharmacology 27: 46–51, 1987PubMedCrossRefGoogle Scholar
  13. Sonnemann E. Allgemeine Lösungen multipler Testprobleme. EDV in Medizin und Biologie 13: 120–128, 1982Google Scholar
  14. Sophianopoulos JA, Durham SJ, Sophianopoulos AJ, et al. Ultrafiltration is theoretically equivalent to equilibrium dialysis but much simpler to carry out. Archives of Biochemistry and Biophysics 187: 132–139, 1978PubMedCrossRefGoogle Scholar
  15. Trenk D, Wagner F, Jähnchen E, Plänitz V. Pharmacokinetics of moxonidine after single and repeated daily doses in healthy volunteers. Journal of Clinical Pharmacology 27: 988–993, 1987PubMedGoogle Scholar
  16. Wellstein A, Palm D, Belz GG, Pitschner HF. Receptor binding characteristics and pharmacokinetic properties as a tool for the prediction of clinical effects of β-blockers. Arzneimittel-Forschung 35(1): 2–6, 1985PubMedGoogle Scholar

Copyright information

© ADIS Press Limited 1988

Authors and Affiliations

  • W. Kirch
    • 1
    • 2
  • H. J. Hutt
    • 1
    • 2
  • V. Plänitz
    • 1
    • 2
  1. 1.Medical DepartmentUniversity of EssenFederal Republic of Germany
  2. 2.Clinical ResearchBeiersdorf AGHamburgFederal Republic of Germany
  3. 3.Medical HospitalChristian Albrechts-UniversitätSchittenhelmstrasse 12KielFederal Republic of Germany

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