Abstract
Single doses of oral and intravenous furosemide were given to 8 healthy male volunteers (40 mg) and 11 patients with renal failure maintained on continuous ambulatory peritoneal dialysis (CAPD) (80 mg). In the volunteers, absorption was variable. Only one half of the intravenous dose and one third of the oral dose was available for renal pharmacological action as judged by the urinary recovery. In the patients, absorption was also variable and was markedly delayed (t max 128 vs 90 min) but more complete (bioavailability 70.1 vs 53.6%). The differences between the two groups were not significant, however (95% C.I.: -90 to 30 and -40.4 to 7.5 respectively). The mean elimination half-life was significantly longer in the patients following both the oral (228 vs 65.1 min) and intravenous dose (195 vs 60.3 min). The total body clearance of furosemide in the volunteers was 138 ml·min−1 and this was much lower in the CAPD patients (61.9 ml·min−1) in whom the renal clearance was minimal. The peritoneal clearance of furosemide was negligible. Although there were trends indicating differences in absorption between the two groups, the significant differences in furosemide disposition observed in CAPD patients were due to renal failure.
Similar content being viewed by others
References
Allison ME, Kennedy AC (1971) Diuretics in chronic renal disease: a study of high dose furosemide. Clin Sci 41:71–187
Chennavasin P, Seiwell R, Brater DC, Liang WMM (1979) Pharmacodynamic analysis of the furosemide-probenecid interaction in man. Kidney Int 16:187–195
Odlind B (1983) Determinants of access of diuretics to their site of action. Fed Proc 42:1703–1706
Rose HJ, O'Malley K, Pruitt AW (1976) Depression of renal clearance of furosemide in man by azotemia. Clin Pharmacol Ther 21:141–146
Brater DC, Anderson SA, Brown-Cartwright D (1986) Response to furosemide in chronic renal insufficiency: rationale for limited doses. Clin Pharmacol Ther 40:134–139
Bernet LZ (1979) Pharmacokinetics/pharmacodynamics of furosemide in man A review. J Pharmacokinet Biopharm 7:1–27
Boles Ponto LL, Schoenwald RD (1990) Furosemide (frusemide). A pharmacokinetic/pharmacodynamic review, part 1. Clin Pharmacokinet 18:381–408
Paton TW, Cornish WR, Manuel MA, Hardy BG (1985) Drug therapy in patients undergoing peritoneal dialysis. Clinical Pharmacokinetic considerations. Clin Pharmacokinet 10:404–426
Lin ET, Smith DE, Bernet LE, Hoener B-A (1979) High-performance liquid chromatographic assays for furosemide in plasma and urine. J Chromatography 163:315–321
Hendeles L, Lafrate RP, Weinberger M (1984) A clinical and pharmacokinetic basis for the selection and use of slow release theophylline products. Clin Pharmacokinet 9:95–135
Huang CM, Atkinson AJ, Levin M, Quintanilla A (1975) Pharmacokinetics of furosemide in advanced renal failure. Clin Pharmacol Ther 16:659–666
Boutron HF, Brocard JF, Singlas E, Charpentier B, Fries D (1981). Pharmacokinetics of furosemide in CAPD. In: Gahl GM, Kessel M, Nolph KD (ed) Advances in peritoneal dialysis: Proceedings of the Second International Symposium on Peritoneal Dialysis, Berlin. Excerpta Medica, Amsterdam, pp 90–92
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
De Paoli Vital E, Casol C, Tessarin C, Tissone GF, Cavagna R (1981) Pharmacokinetics of digoxin in CAPD. In: Gahl GM, Kessel M, Nolph KD (ed) Advances in peritoneal dialysis: Proceedings of the Second International Symposium on Peritoneal Dialysis, Berlin. Excerpta Medica, Amsterdam, pp 85–87
Bush A, Holt JE, Sankey MG, Kaye CM, Gabriel R (1983) Penetration of metronidazole into continuous ambulatory peritoneal dialysate. Perit Dial Bull 3:176–177
Grech-Belanger O, Langlois S, Leboeuf E (1988) Pharmacodynamics of diltiazem in patients undergoing continuous ambulatory peritoneal dialysis. J Clin Pharmacol 28:477–480
Chapman JR, Warbock DW (1983) Ketoconazole and fungal CAPD peritonitis. Lancet II:510–511
Andreasen F, Christensen CK, Jakobsen FK, Jansen J, Morgensen CE, Pederson OL (1982) The individual variation in pharmacokinetics and pharmacodynamics of furosemide in young male subjects. Eur J Clin Invest 12:247–255
Branch RA, Roberts CJC, Homeida M, Levine D (1977) Determinants of response to frusemide in man. Br J Clin Pharmacol 4:121–127
Hammarlind MM, Paalzow LK, Odlind B (1984) Pharmacokinetics of furosemide in man after intravenous and oral administration. Application of moment analysis. Eur J Clin Pharmacol 26:197–207
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
Rane A, Villeneuve JP, Stone WJ, Nies AS, Wilkinson GR, Branch RA (1978) Plasma binding and disposition of furosemide in the nephrotic syndrome and in uremia. Clin Pharmacol Ther 24:199–207
Voelker JR, Cartwright-Brown D, Anderson S, Leinfelder J, Sica DA, Kokko J, Brater DC (1987) Comparison of loop diuretics in patients with chronic renal insufficiency. Kidney Int 32:572–578
Beermann B, Dalen E, Lindstrom B, Rosen A (1977) Elimination of furosemide in healthy subjects and in those with renal failure. Clin Pharmacol Ther 22:70–78
Branch RA (1983) Role of binding in distribution of furosemide: where is non-renal clearance? Fed Proc 42:1699–1702
Verbeeck RK, Patwardhan RV, Villeneuve J-P, Wilkinson GR, Branch RA (1982) Furosemide disposition in cirrhosis. Clin Pharmacol Ther 31:719–725
Keller E, Reetze P, Schollmeyer P (1990) Drug therapy in patients undergoing continuous ambulatory peritoneal dialysis: clinical pharmacokinetic considerations. Clin Pharmacokinet 18:104–117
Peterson LR, Gerding DN (1980) Influence of protein binding of antibiotics on serum pharmacokinetics and extravascular penetration: clinically useful concepts. Rev Infect Dis 2:340–34
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Martin, U., Prescott, L.F. & Winney, R.J. Furosemide disposition in patients on CAPD. Eur J Clin Pharmacol 48, 385–390 (1995). https://doi.org/10.1007/BF00194955
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00194955