Furosemide pharmacokinetics

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

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. 

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. 

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. 

Muzolimine (710), a 1-substituted 2-pyrazolin-5-one derivative, is a highly active diuretic, differing from the structures of other diuretics since it contains neither a sulfonamide nor a carboxyl group. It has a saluretic effect similar to furosemide and acts in the proximal tubule and in the medullary portion of the ascending limb of the loop of Henle. Pharmacokinetic studies in dogs, healthy volunteers and in patients with renal insufficiency show that the compound is readily absorbed after oral administration (B-80MI40406). 

Loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid) are all equally effective when given in equivalent doses. Therefore, selection is based on the side-effect profile, cost, and pharmacokinetics of the agents. The incidence of ototoxicity is significantly higher with ethacrynic acid compared to the other loop diuretics therefore, its use is limited to patients who are allergic to the sulfa component in the other loop diuretics.15 While ototoxicity is a well-established side effect of furosemide, its incidence is greater when administered by the intravenous route at a rate exceeding 4 mg per minute.16 Torsemide has not been reported to cause ototoxicity. 

There are several pharmacokinetic differences between loop diuretics. Fifty to sixty percent of a dose of furosemide is excreted unchanged by the kidney with the remainder undergoing glucuronide conjugation in the kidney.17 In contrast, liver metabolism accounts for 50% and 80% of the elimination of bumetanide and torsemide, respectively.17 Thus, patients with ARF may have a prolonged half-life of furosemide. The bioavailability of both torsemide and bumetanide is higher than for furosemide. The intravenous (IV) oral ratio for bumetanide and torsemide is 1 1, bioavailability of oral furosemide is approximately 50%, with a reported range of 10% to 100%.18... 

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

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

Pharmacokinetics These agents are metabolized and excreted primarily through the urine. Protein binding of these agents exceeds 90%. Furosemide is metabolized approximately 30% to 40%, and its urinary excretion is 60% to 70%. Oral administration of bumetanide revealed that 81% was excreted in urine, 45% of it as unchanged drug. Torsemide is cleared from the circulation by both hepatic metabolism (approximately 80% of total clearance) and excretion into the urine (approximately 20% of total clearance). ... 

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. 

The sites of action within the kidney and the pharmacokinetics of various diuretic drugs are discussed in Chapter 15. Thiazide diuretics are appropriate for most patients with mild or moderate hypertension and normal renal and cardiac function. More powerful diuretics (eg, those acting on the loop of Henle) such as furosemide are necessary in severe hypertension, when multiple drugs with sodium-retaining properties are used in renal insufficiency, when glomerular filtration rate is less than 30 or 40 mL/min and in cardiac failure or cirrhosis, in which sodium retention is marked. 

Pharmacokinetic studies showed that 30 min after oral administration of 20 mg furosemide/kg bw in dogs, 22.73 ppb was the maximum plasma concentration attained. The oral bioavailability of the compound was estimated at approximately 77%. Furosemide is extensively bound to plasma proteins (91%). In dogs, the elimination half-life of furosemide was found to be 1.42 h after oral dosing, and... 

One interesting pharmacokinetic phenomenon observed with tasidotin was that parent concentrations prior to ending the infusion were higher than at the end of the infusion (Fig. 13.9). For a drug with constant clearance, this should not be possible. Although unusual, this phenomenon is not unheard of, having been reported for suberoylanilide hydroxamic acid, a histone deacetylase inhibitor [26]. In that report, the authors could not postulate a reason for such pharmacokinetic behavior. The same effect has also been reported for furosemide, perhaps due to the drug s behavior within the renal tubule [27]. 

Huang CM, Atkinson AJ Jr, Levin M, Levin NW, Quintanilla A. Pharmacokinetics of furosemide in advanced renal failure. Clin Pharmacol Ther 1974 16 659-66. 

Brunner, G., Bergmann, von, K., Hacker, W., Mdllendorff, von, E. Comparison of diuretic effects and pharmacokinetics of torasemid and furosemid after a single oral dose in patients with hydropically decompensated cirrhosis of the liver. Arzneim. Forsch. 1988 38 176-179... 

Lawson DH, Tilstone WJ, Gray JM, Srivastava PK. Effect of furosemide on the pharmacokinetics of gentamicin in patients. J Chn Pharmacol 1982 22(5-6) 254-8. 

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

In a similar vein, Leehey et al. [201] have reported on the frequency of aminoglycoside-induced nephrotoxicity using three different dosing schemes, including two that were based on pharmacokinetic principles. It is noteworthy that despite careful calculation of the dosing scheme, this did not alter the incidence of nephrotoxicity. However, the duration of dosing correlated positively with nephrotoxicity incidence, as did treatment with furosemide, old age, and liver disease. 

Furosemide (Lasix) Route PO/IM/IV Pregnancy category C Pharmacokinetic Well absorbed from GI tract. PB 91%-97% metabolized in liver excreted in urine (in severe renal impairment, nonrenal clearance... 

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... 

The AASLD practice guidelines recommend that diuretic therapy be initiated with the combination of spironolactone and furosemide. Spironolactone alone was commonly recommended for initial therapy, but clinical trials have demonstrated a 14-day delay in the onset of action, as well as the development hyperkalemia when spironolactone is used alone. Administering spironolactone in single daily doses is justified based on its pharmacokinetics and helps to improve patient compliance. If tense ascites is present, paracentesis... 

Vree, T.B. Van den Bi elaar-Martea, M. Verwey-van Wissen, C.P.W.G.M. Determination of furosemide with its acyl glucoronide in human plasma and urine hy means of direct gradient high-performance liquid chromatographic anedysis with fluorescence detection. Preliminary pharmacokinetics and effect of probenecid. J.Chromatogr.B, 1994, 656, 53—62... 

Saugy, M. Meuwly, R Munafo, A. Rivier, L. Rapid high-performance liquid chromatographic determination with fluorescence detection of furosemide in human body fluids and its confirmation by gas chromatography-mass spectrometry. J.Chromatogr., 1991, 564, 567-578 [serum urine fluorescence detection warfarin (IS) pharmacokinetics gradient LOD 10 ng/mL]... 

Probenecid but not cidofovir alters zidovudine pharmacokinetics such that zidovudine doses should be reduced when probenecid is present, as should the doses of drugs similarly affected by probenecid fe.g., /i-lactam antibiotics, nonsteroidal anti-inflammatory drugs [NSAIDs], acyclovir, lorazepam, furosemide, methotrexate, theophylline, and rifampin). Concurrent nephrotoxic agents are contraindicated, and an interval of 1 week before beginning cidofovir treatment is recommended after prior exposure to aminoglycosides, intravenous pentamidine, amphotericin foscamet, NSAIDs, or contrast dye. Cidofovir and oral ganciclovir in combination are poorly tolerated at full doses. 

The chiorine and suifonamide substitutions are features aiso seen in previousiy discussed diuretics. Because the moiecuie possesses a free carboxyi group, furosemide is a stronger acid than the thiazide diuretics (pKa = 3.9). This drug is excreted primariiy unchanged. A smaii amount of metaboiism, however, can take piace on the furan ring, which is substituted on the aromatic amino group (see Tabie 27.2 for its other pharmacokinetic properties). 

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