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. 1993 Feb;35(2):128–135.

Effect of renal function on the pharmacokinetics and pharmacodynamics of trandolapril.

E G Bevan 1, G T McInnes 1, J C Aldigier 1, J J Conte 1, J P Grunfeld 1, S J Harper 1, B H Meyer 1, N Pauly 1, R Wilkinson 1
PMCID: PMC1381503  PMID: 8443030

Abstract

1. The pharmacokinetics and pharmacodynamics of a single dose of trandolapril, an angiotensin converting enzyme (ACE) inhibitor with an active metabolite, trandolaprilat, which is in part further metabolised prior to renal elimination, were evaluated in 31 subjects with a wide range of renal function (creatinine clearance 4-112 ml min-1 1.73 m-2). 2. The pharmacokinetics of trandolapril were unaffected by differences in renal function. 3. In contrast, there was a close correlation between the renal clearance (0-96 h) of trandolaprilat and creatinine clearance (r = 0.95, P = 0.0001). The maximum plasma concentration of trandolaprilat, and the area under the concentration curve (0-96 h) correlated inversely with creatinine clearance (r = -0.59, P < 0.001; and r = -0.61, P < 0.001 respectively). 4. Significant changes in plasma trandolaprilat concentrations were seen only in patients with creatinine clearances of 30 ml min-1 1.73 m-2 or less, suggesting that a dose reduction in trandolapril might be advisable in severe renal impairment. 5. However, the majority of parameters of ACE inhibition were unrelated to creatinine clearance, although area under the curve for ACE inhibition (0-336 h) showed a weak negative correlation (r = -0.49, P < 0.01). Similarly, weighted mean changes in blood pressure were not influenced by renal function. 6. Therefore, while the pharmacokinetic parameters of trandolaprilat correlated with creatinine clearance, pharmacodynamic measurements (ACE inhibition and blood pressure changes) in general showed no such relationship, indicating that dose adjustment of ACE inhibitors in renal impairment should be based on pharmacokinetic results only in conjunction with pharmacodynamic data.

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Selected References

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  1. Begg E. J., Bailey R. R., Lynn K. L., Robson R. A., Frank G. J., Olson S. C. The pharmacokinetics of angiotensin converting enzyme inhibitors in patients with renal impairment. J Hypertens Suppl. 1989 Sep;7(5):S29–S32. [PubMed] [Google Scholar]
  2. Begg E. J., Robson R. A., Bailey R. R., Lynn K. L., Frank G. J., Olson S. C. The pharmacokinetics and pharmacodynamics of quinapril and quinaprilat in renal impairment. Br J Clin Pharmacol. 1990 Aug;30(2):213–220. doi: 10.1111/j.1365-2125.1990.tb03767.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Breckenridge A. Angiotensin converting enzyme inhibitors. Br Med J (Clin Res Ed) 1988 Feb 27;296(6622):618–620. doi: 10.1136/bmj.296.6622.618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chevillard C., Brown N. L., Jouquey S., Mathieu M. N., Laliberté F., Hamon G. Cardiovascular actions and tissue-converting enzyme inhibitory effects of chronic enalapril and trandolapril treatment of spontaneously hypertensive rats. J Cardiovasc Pharmacol. 1989 Aug;14(2):297–301. doi: 10.1097/00005344-198908000-00017. [DOI] [PubMed] [Google Scholar]
  5. Chevillard C., Brown N. L., Mathieu M. N., Laliberté F., Worcel M. Differential effects of oral trandolapril and enalapril on rat tissue angiotensin-converting enzyme. Eur J Pharmacol. 1988 Feb 16;147(1):23–28. doi: 10.1016/0014-2999(88)90629-2. [DOI] [PubMed] [Google Scholar]
  6. Debusmann E. R., Pujadas J. O., Lahn W., Irmisch R., Jané F., Kuan T. S., Mora J., Walter U., Eckert H. G., Hajdú P. Influence of renal function on the pharmacokinetics of ramipril (HOE 498). Am J Cardiol. 1987 Apr 24;59(10):70D–78D. doi: 10.1016/0002-9149(87)90057-9. [DOI] [PubMed] [Google Scholar]
  7. Farrow P. R., Wilkinson R. Reversible renal failure during treatment with captopril. Br Med J. 1979 Jun 23;1(6179):1680–1680. doi: 10.1136/bmj.1.6179.1680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fillastre J. P., Moulin B., Godin M., Williams P. E., Brown A. N., Francis R. J., Pinta P., Manfredi R. Pharmacokinetics of cilazapril in patients with renal failure. Br J Clin Pharmacol. 1989;27 (Suppl 2):275S–282S. doi: 10.1111/j.1365-2125.1989.tb03492.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Harjanne A. Automated kinetic determination of angiotensin-converting enzyme in serum. Clin Chem. 1984 Jun;30(6):901–902. [PubMed] [Google Scholar]
  10. Hricik D. E., Browning P. J., Kopelman R., Goorno W. E., Madias N. E., Dzau V. J. Captopril-induced functional renal insufficiency in patients with bilateral renal-artery stenoses or renal-artery stenosis in a solitary kidney. N Engl J Med. 1983 Feb 17;308(7):373–376. doi: 10.1056/NEJM198302173080706. [DOI] [PubMed] [Google Scholar]
  11. Kelly J. G., Doyle G., Donohue J., Laher M., Vandenburg M. J., Currie W. J., Cooper W. D. Pharmacokinetics of enalapril in normal subjects and patients with renal impairment. Br J Clin Pharmacol. 1986 Jan;21(1):63–69. doi: 10.1111/j.1365-2125.1986.tb02823.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kostis J. B. Angiotensin converting enzyme inhibitors. I. Pharmacology. Am Heart J. 1988 Dec;116(6 Pt 1):1580–1591. doi: 10.1016/0002-8703(88)90747-8. [DOI] [PubMed] [Google Scholar]
  13. Patat A., Surjus A., Le Go A., Granier J. Safety and tolerance of single oral doses of trandolapril (RU 44.570), a new angiotensin converting enzyme inhibitor. Eur J Clin Pharmacol. 1989;36(1):17–23. doi: 10.1007/BF00561017. [DOI] [PubMed] [Google Scholar]
  14. Rotmensch H. H., Vlasses P. H., Ferguson R. K. Angiotensin-converting enzyme inhibitors. Med Clin North Am. 1988 Mar;72(2):399–425. doi: 10.1016/s0025-7125(16)30776-3. [DOI] [PubMed] [Google Scholar]
  15. Till A. E., Gomez H. J., Hichens M., Bolognese J. A., McNabb W. R., Brooks B. A., Noormohamed F., Lant A. F. Pharmacokinetics of repeated single oral doses of enalapril maleate (MK-421) in normal volunteers. Biopharm Drug Dispos. 1984 Jul-Sep;5(3):273–280. doi: 10.1002/bdd.2510050309. [DOI] [PubMed] [Google Scholar]
  16. Williams G. H. Converting-enzyme inhibitors in the treatment of hypertension. N Engl J Med. 1988 Dec 8;319(23):1517–1525. doi: 10.1056/NEJM198812083192305. [DOI] [PubMed] [Google Scholar]

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