Furosemide pharmacodynamics

LLB Ponto, RD Schoenwald. Furosemide A pharmacokinetics/pharmacodynamics review. Clin Pharmacok 18 381-408, 1993. 

L. Z., Furosemide pharmacokinetics and pharmacodynamics in health and disease - an update, J. Pharmacokinet. Biopharm. 1989, 37, 1-46. 

Ponto, L. L., Schoenwald, R. D., Furosemide (frusemide). A pharmacokinetic/pharmacodynamic review (Part I), Clin. Pharmacokinet. 1990, 38, 381-408. 

Wakelkamp M, Alvan G, Gabrielsson J, Paintaud G. Pharmacodynamic modeling of furosemide tolerance after multiple intravenous administration. Clin Pharmacol Ther 1996 60 75-88. 

Bindschedler M., P. Degen, G. Flesch, M. de Gasparo, and G. Preiswerk (1997). Pharmacokinetics and pharmacodynamic interaction of single oral doses of valsartan and furosemide. European Journal of Clinical Pharmacology 52 371-378. 

Klausner, E. A., Lavy, E., Stepensky, D. et al. Furosemide pharmacokinetics and pharmacodynamics following gastroretentive dosage form administration to healthy volunteers. J. Clin. Pharmacol. 43(7) 711-720, 2003. 

FIGURE 19.7 The diuretic effect of furosemide is to increase the excretion rate of sodium. The pharmacodynamics of furosemide show a steep concentration effect relationship, with a clear maximum effect (180 mmol/hr of Na+). The EC q is 1.5 mg/L and the Hill coefficient (n) is 3. 

Furosemide is a widely used loop diuretic indicated for the treatment of different pathological conditions such as congestive heart failure, hepatic cirrhosis, and chronic renal failure. It has a narrow absorption window and mainly absorbed from the stomach and the upper part of the small intestine. Following administration of furosemide, the natriuretic effect rapidly disperses and is concealed before the next administration. This problematic aspect in furosemide therapy is mostly attributed to the natural homeostatic compensatory mechanisms. Lately, it has been demonstrated that the diuretic and natriuretic effects of furosemide can be significantly improved, following a continuous input (intravenous infusion) compared to immediate release DFs. Beside the narrow absorption window, this pharmacodynamic feature of the drug provides another rationale for the development of a GRDF for furosemide. 

Klausner, E.A. Lavy, E. Stepensky, D. Friedman, M. Hoffman, A. Novel gastroretentive dosage forms evaluation of gastroretentivity and its effect on Levodopa absorption in humans. Pharm. Res. 2003,20 (9), 1466-1473. Klausner, E.A. Lavy, E. Stepensky, D. Cserepes, E. Barta, M. Friedman, M. Hoffman, A. Furosemide pharmacokinetics and pharmacodynamics following gastroretentive dosage form administration to healthy volunteers. J. Clin. Pharmacol 2003, 43, 711-720. 

Benet LZ. Pharmacokinetics/pharmacodynamics of furosemide in man a review. J Pharmacokinet Biopharm 1979 7(l) l-27. 

Pharmacokinetic studies of triamterene in combination with other drugs have also been done. In human subjects pharmacokinetics of triamterene with xipamide, 8 with hydrochlorothiazide,69 with propranolol and hydrochlorothiazide combination,70 and with oxprenolol and hydrochlorothiazide combination,71 have been studied. Pharmacokinetic and pharmacodynamic studies of the combination of furosemide retard and triamterene have been done in detail in healthy volunteers.72-75 In another study triamterene is reported to reduce the extrarenal elimination of digoxin, but induced no changes in digoxin-elicited inotropy.76... 

Bindschedler D en P, Flesch G, de Gasparo M, Preisweric G. Fliarmacokinetic and pharmacodynamic interaction of sii le oral doses of valsartan and furosemide. EurJClin Phcuma-co/(1997) 52,371-8. 

Meloxicam 15 mg daily for 3 days had no significant effect on the pharmacokinetics of furosemide 40 mg in 12 healthy subjects. The furosem-ide-induced diuresis was unchanged, and although the cumulative urinary electrolyte excretion was somewhat lower, but this was not considered to be clinically significant.A similar study in patients with heart failure taking an ACE inhibitor also found no clinically significant pharmacokinetic or pharmacodynamic interaction between furosemide and meloxicam. 

Muller FO, Schall R, de Vaal AC, Groenewoud G, Hundt HKL, hfrddle MV. Influence of meloxicam on furosemide pharmacokinetics and pharmacodynamics in healthy volunteers. EurJ Clin Pharmacol (1995) 48, 247-51. 

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