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British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1988 Nov;26(5):557–562. doi: 10.1111/j.1365-2125.1988.tb05295.x

Effect of indomethacin on the pharmacokinetics and pharmacodynamics of felodipine.

B G Hardy 1, W R Bartle 1, M Myers 1, D G Bailey 1, B Edgar 1
PMCID: PMC1386632  PMID: 3207560

Abstract

1. We studied the effects of pre-treatment with oral indomethacin (25 mg four times daily for 3 days) on the pharmacokinetics, haemodynamics and diuretic properties of oral felodipine (10 mg single dose) in 12 healthy male volunteers using a placebo controlled double-blind four-way crossover protocol. 2. Felodipine with or without indomethacin pretreatment reduced standing diastolic blood pressure (P less than 0.001) at 0.5 to 3.0 h after dosing compared with placebo or indomethacin alone. Systolic blood pressures during indomethacin treatment alone were consistently higher than the other three treatment groups (P less than 0.01), presumably due to sodium and fluid retention. 3. Felodipine and felodipine plus indomethacin produced significantly greater excretion of urine and urinary sodium, but not of urinary potassium or creatinine when compared with placebo (P less than 0.01) over an 8 h period. 4. The pharmacokinetic parameters of felodipine (Cmax, tmax, t1/2 and AUC), the concentration-response curves for blood pressure lowering effects, the reflex tachycardia, diuretic properties and side-effects profile of felodipine were not significantly altered by indomethacin pretreatment in normal volunteers.

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Selected References

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  1. Ahnoff M. Determination of felodipine in plasma by capillary gas chromatography with electron capture detection. J Pharm Biomed Anal. 1984;2(3-4):519–526. doi: 10.1016/0731-7085(84)80055-2. [DOI] [PubMed] [Google Scholar]
  2. DiBona G. F. Effects of felodipine on renal function in animals. Drugs. 1985;29 (Suppl 2):168–175. doi: 10.2165/00003495-198500292-00031. [DOI] [PubMed] [Google Scholar]
  3. Edgar B., Regårdh C. G., Johnsson G., Johansson L., Lundborg P., Löfberg I., Rönn O. Felodipine kinetics in healthy men. Clin Pharmacol Ther. 1985 Aug;38(2):205–211. doi: 10.1038/clpt.1985.160. [DOI] [PubMed] [Google Scholar]
  4. Feely J., Wood A. J. Effect of inhibitors of prostaglandin synthesis on hepatic drug clearance. Br J Clin Pharmacol. 1983 Jan;15(1):109–111. doi: 10.1111/j.1365-2125.1983.tb01472.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Katzman P. L., Hulthén U. L., Hökfelt B. The effect of 8 weeks treatment with the calcium antagonist felodipine on blood pressure, heart rate, working capacity, plasma renin activity, plasma angiotensin II, urinary catecholamines and aldosterone in patients with essential hypertension. Br J Clin Pharmacol. 1986 Jun;21(6):633–640. doi: 10.1111/j.1365-2125.1986.tb05227.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Mace P. J., Stallard T. J., Littler W. A. Felodipine in hypertension. Eur J Clin Pharmacol. 1985;29(4):383–389. doi: 10.1007/BF00613449. [DOI] [PubMed] [Google Scholar]
  7. Maclean D., Mitchell E. T., Readman A. S. Felodipine compared to nifedipine as "third-line drug" in resistant hypertension. Angiology. 1986 Nov;37(11):840–845. doi: 10.1177/000331978603701108. [DOI] [PubMed] [Google Scholar]
  8. Rönn O., Bengtsson B., Edgar B., Raner S. Acute haemodynamic effects of felodipine and verapamil in man, singly and with metoprolol. Drugs. 1985;29 (Suppl 2):16–25. doi: 10.2165/00003495-198500292-00005. [DOI] [PubMed] [Google Scholar]
  9. Sheridan J. V., Thomas P., Routledge P. A., Sheridan D. J. Effects of felodipine on haemodynamics and exercise capacity in patients with angina pectoris. Br J Clin Pharmacol. 1987 Apr;23(4):391–396. doi: 10.1111/j.1365-2125.1987.tb03067.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Sluiter H. E., Huysmans F. T., Thien T. A., van Lier H. J., Koene R. A. Haemodynamic, hormonal, and diuretic effects of felodipine in healthy normotensive volunteers. Drugs. 1985;29 (Suppl 2):26–35. doi: 10.2165/00003495-198500292-00006. [DOI] [PubMed] [Google Scholar]
  11. Smith S. A., Mace P. J., Littler W. A. Felodipine, blood pressure, and cardiovascular reflexes in hypertensive humans. Hypertension. 1986 Dec;8(12):1172–1178. doi: 10.1161/01.hyp.8.12.1172. [DOI] [PubMed] [Google Scholar]
  12. Steiness E., Waldorff S. Different interactions of indomethacin and sulindac with thiazides in hypertension. Br Med J (Clin Res Ed) 1982 Dec 11;285(6356):1702–1703. doi: 10.1136/bmj.285.6356.1702-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sullivan J. M. Prostaglandins and regulation of blood pressure: clinical implications. Pharmacol Ther. 1981;15(3):447–465. doi: 10.1016/0163-7258(81)90054-1. [DOI] [PubMed] [Google Scholar]
  14. Unadkat J. D., Bartha F., Sheiner L. B. Simultaneous modeling of pharmacokinetics and pharmacodynamics with nonparametric kinetic and dynamic models. Clin Pharmacol Ther. 1986 Jul;40(1):86–93. doi: 10.1038/clpt.1986.143. [DOI] [PubMed] [Google Scholar]
  15. Wilkin J. K. Flushing reactions: consequences and mechanisms. Ann Intern Med. 1981 Oct;95(4):468–476. doi: 10.7326/0003-4819-95-4-468. [DOI] [PubMed] [Google Scholar]
  16. Yeh K. C., Kwan K. C. A comparison of numerical integrating algorithms by trapezoidal, Lagrange, and spline approximation. J Pharmacokinet Biopharm. 1978 Feb;6(1):79–98. doi: 10.1007/BF01066064. [DOI] [PubMed] [Google Scholar]

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