Summary
The bioavailability and diuretic effect of furosemide 40 mg administered orally for at least 6 months have been compared in patients with chronic respiratory failure and in healthy controls. The mean urinary recovery of unchanged drug was 11.5 mg and 9.41 mg in 24 h after pre- and postprandial administration to 10 patients, whereas the recovery was 14.4 mg in 10 healthy subjects. The diuretic effect, in terms of urine flow and sodium ion excretion in the 6 h after administration, was also less in patients than in healthy subjects. This was ascribed to the lower bioavailability of furosemide in patients, based on the urinary recovery of unchanged drug, and not to a lower level of response to furosemide than in healthy subjects. The mean absolute bioavailability of furosemide in 6 patients was 41.3% and 63.4%, respectively, calculated from unchanged drug and total drug (unchanged plus glucuronide conjugate). Approximately 53.9% of the dose of furosemide was excreted as the glucuronide conjugate after oral administration, and 34.2% after i.v. injection in the 6 patients. In 3 of the 6 patients studied, a distinct first-pass effect for glucuronidation of furosemide was observed after oral administration. In another study, the mean glucuronide fraction recovered in 24-h urine was 20.7% and 7.3% (p<0.01) in 38 patients and 12 healthy subjects, respectively. The fraction in urine was not affected by changing the dose of furosemide from 20 to 120 mg. The lower bioavailability in patients as compared to healthy subjects is ascribed to enhanced glucuronidation and incomplete drug absorption.
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Ogata H, Zugarni S, Ejima A, Kawatsu Y (1983) Bioavailability of two preparations of furosemide and their pharmacological activity in normal volunteers. Eur J Clin Pharmacol 24: 791–796
Beermann B, Dalen E, Lindstrom B, Rosen A (1975) On the fate of furosemide in man. Eur J Clin Pharmacol 9: 57–61
Fuller R, Hoppel C, Ingalls ST (1981) Furosemide kinetics in patients with hepatic cirrhosis with ascites. Clin Pharmacol Ther 30: 461–467
Huang CM, Atkinson AJ, Levin M, Levin NW, Quintanilla A (1974) Pharmacokinetics of furosemide in advanced renal failure. Clin Pharmacol Ther 16: 659–666
Rose HJ, O'Malley K, Pruitt AW (1976) Depression of renal clearance of furosemide in man by azotemia. Clin Pharmacol Ther 21: 141–146
Beermann B, Dalen E, Lindstrom B (1977) Elimination of furosemide in healthy subjects and in those with renal failure. Clin Pharmacol Ther 22: 70–78
Andreasen F, Hansen HE, Mikkelsen E (1978) Pharmacokinetics of furosemide in anephric patients and in normal subjects. Eur J Clin Pharmacol 13: 41–48
Riva E, Fossali E, Bettinelli A (1982) Kinetics of furosemide in children with chronic renal failure undergoing regular haemodialysis. Eur J Clin Pharmacol 21: 303–306
Allgulander C, Beermann B, Sjogren A (1980) Frusemide pharmacokinetics in patients with liver disease. Clin Pharmacol Ther 5: 570–575
Keller E, Hoppe-Seyler G, Mumm R, Schollmeyer P (1981) Influence of hepatic cirrhosis and end-stage renal disease on pharmacokinetics and pharmacodynamics of furosemide. Eur J Clin Pharmacol 20: 27–33
Verbeeck RK, Patwardhan RV, Villeneuve JP, Wilkinson GR, Branch RA (1982) Furosemide disposition in cirrhosis. Clin Pharmacol Ther 31: 719–725
Gonzalez G, Arancibia A, Rivas MI, Caro P, Antezana C (1982) Pharmacokinetics of furosemide in patients with hepatic cirrhosis. Eur J Clin Pharmacol 22: 315–320
Branch RA, Roberts CJC, Homeida M, Levine D (1977) Determinations of response to frusemide in normal subjects. Br J Clin Pharmacol 4: 121–127
Waller ES, Hamilton SF, Massarella JW, Sharanevych MA, Smith RV, Yakatan GJ, Doluisio JT (1982) Disposition and absolute bioavailability of furosemide in healthy males. J Pharm Sci 71: 1105–1108
Kelly MR, Cutler RE, Forrey AW, Kimpel BM (1973) Pharmacokinetics of orally administered furosemide. Clin Pharmacol Ther 15: 178–186
Benet LZ (1979) Pharmacokinetics/pharmacodynamics of furosemide in man: a review. J Pharmacokinet Biopharm 7: 1–27
Fine A, Henderson IS, Morgan DR, Tilstone WJ (1977) Malabsorption of furosemide caused by phenytoin. Brit Med J: 1061–1062
Riva E, Farina P, Tognoni G, Bottino S, Orrico C, Pardi G (1978) Pharmacokinetics of furosemide in gestosis of pregnancy. Eur J Clin Pharmacol 14: 361–366
Brown DD, Juhl RP (1976) Decreased bioavailability of digoxin due to antacids and kaolin-pectin. N Engl J Med 295: 1034–1037
Uribe M, Casian C, Rojas S, Sierra JG, Go VLM (1981) Decreased bioavailability of prednisone due to antacids in patients with chronic active liver disease and in healthy volunteers. Gastroenterology 80: 661–665
Verbeeck R, Tjandramaga TB, Mullie A, Verbesselt R, De Schepper PJ (1979) Effect of aluminum hydroxide on diflunisal absorption. Br J Clin Pharmacol 7: 519–522
Smith DE, Lin ET, Benet LZ (1980) Absorption and disposition of furosemide in healthy volunteers, measured with a metabolite-specific assay. Drug Metab Dispos 8: 337–342
Andreasen F, Mikkelsen E (1977) Distribution, elimination and effect of furosemide in normal subjects and in patients with heart failure. Eur J Clin Pharmacol 12: 15–22
Andreasen F, Pedersen OL, Mikkelsen E (1978) Distribution, elimination and natriuretic effect of furosemide in patients with severe arterial hypertension. Eur J Clin Pharmacol 14: 237–244
Andreasen F, Hausen U, Husted SE, Jansen JA (1983) The pharmacokinetics of frusemide are influenced by age. Br J Clin Pharmacol 16: 391–397
Kelly MR, Blair AD, Forrey AW, Smidt NA, Cutler RE (1977) A comparison of the diuretic response to oral and intravenous furosemide in “diuretic-resistant” patients. Curr Ther Res 21: 1–9
Kaojarern S, Day B, Brater DC (1982) The time course of delivery of furosemide into urine: An independent determinant of overall response. Kidney Int 22: 69–74
Uchino K, Isozaki S, Amano J, Tanaka N, Saitoh Y, Nakagawa F, Tamura Z, Oka H (1983) Clinical pharmacokinetics and diuretic effect of furosemide on plain tablet and retard capsule with normal subjects and cirrhotic patients. J Pharm Dyn 6: 684–691
Ebihara A, Oka T (1983) Pharmacodynamic and pharmacokinetic study of a slow-release formulation of furosemide in man. Arzneimittelforsch/Drug Res 33: 163–166
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Ogata, H., Kawatsu, Y., Maruyama, Y. et al. Bioavailability and diuretic effect of furosemide during long-term treatment of chronic respiratory failure. Eur J Clin Pharmacol 28, 53–59 (1985). https://doi.org/10.1007/BF00635708
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DOI: https://doi.org/10.1007/BF00635708