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European Journal of Clinical Pharmacology

, Volume 26, Issue 2, pp 197–207 | Cite as

Pharmacokinetics of furosemide in man after intravenous and oral administration. Application of moment analysis

  • M. M. Hammarlund
  • L. K. Paalzow
  • B. Odlind
Originals

Summary

Furosemide 40 mg was administered to 8 healthy subjects as an i.v. bolus dose, as 1 tablet in the fasting state, and as 1 tablet and a solution after food intake. The i.v. data gave a total body clearance of 162±10.8 ml/min and a renal clearance of 117±11.3 ml/min; the volume of distribution at steady state was 8.3±0.61. Oral administration gave a bioavailability of the tablet (fasting) of 51%. Food intake slightly reduced the bioavailability, but not to a significant extent. There was no significant difference in availability between the tablet and the solution. Moment analysis gave a mean residence time after the i.v. dose, MRTi.v., of 51±1.5 min. The mean absorption times (MAT) for all oral doses were significantly longer than the MRTi.v., indicating absorption rate-limited kinetics of furosemide. On average, food delayed the absorption by 60 min. The MAT for the tablet in the postprandial state was significantly longer than for the solution, indicating dissolution rate-limited absorption of the tablet.

Key words

furosemide bioavailability pharmacokinetics oral administration i.v. administration drug absorption moment analysis food effect dissolution effect 

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References

  1. 1.
    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: 337–342Google Scholar
  2. 2.
    Waller ES, Hamilton SF, Massarella JW, Sharanevych MA, Smith RV, Yatakan GJ, Dolusio JT (1982) Disposition and absolute bioavailability of furosemide in healthy males. J Pharm Sci 71: 1105–1108Google Scholar
  3. 3.
    Chungi VS, Dittert LW, Smith PB (1979) Gastrointestinal sites of furosemide absorption in rats. Int J Pharm 4: 27–38Google Scholar
  4. 4.
    Hammarlund MM, Paalzow LK (1982) Dose-dependent pharmacokinetics of furosemide in the rat. Biopharm Drug Dispos 3: 345–359Google Scholar
  5. 5.
    Yamaoka K, Nakagawa T, Uno T (1978) Statistical moments in pharmacokinetics. J Pharmacokinet Biopharm 6: 547–558Google Scholar
  6. 6.
    Riegelman S, Collier P (1980) The application of statistical moment theory to the evaluation of in vivo dissolution time and absorption time. J Pharmacokinet Biopharm 8: 509–534Google Scholar
  7. 7.
    Program DARE-MINUIT. Data Dept., Biomedical Center, University of Uppsala, SwedenGoogle Scholar
  8. 8.
    Benet LZ (1979) Pharmacokinetics/pharmacodynamics of furosemide in man: a review. J Pharmacokinet Biopharm 7: 1–126Google Scholar
  9. 9.
    Cutler RE, Blair AD (1979) Clinical pharmacokinetics of furosemide. Clin Pharmacokinet 4: 279–296Google Scholar
  10. 10.
    Rupp W (1974) Pharmacokinetics and pharmacodynamics of Lasix. Scot Med J 19: 5–13Google Scholar
  11. 11.
    Andreasen F, Kjeldahl Christensen C, Kjaer Jacobsen F, Jansen J, Mogensen CE, Lederballe Pedersen O (1982) The individual variation in pharmacokinetics and pharmacodynamics of furosemide in young normal male subjects. Eur J Clin Invest 12: 247–255Google Scholar
  12. 12.
    Benet LZ, Galeazzi RL (1979) Noncompartmental determination of the steady-state volume of distribution. J Pharm Sci 68: 1071–1074Google Scholar
  13. 13.
    Tozer TN (1981) Concepts basic to pharmacokinetics. Pharmacol Ther 12: 109–131Google Scholar
  14. 14.
    Kelly MR, Cutler RE, Forrey AW, Kimpel BM (1974) Pharmacokinetics of orally administered furosemide. Clin Pharmacol Ther 15: 178–186Google Scholar
  15. 15.
    Beermann B (1982) Kinetics and dynamics of furosemide and slow-acting furosemide. Clin Pharmacol Ther 32: 584–591Google Scholar
  16. 16.
    Clements JA, Heading RC, Nimmo WS, Prescott LF (1978) Kinetics of acetaminophen absorption and gastric emptying in man. Clin Pharmacol Ther 24: 420–431Google Scholar
  17. 17.
    Andreasen F, Kjeldahl Christensen C, Kjaer Jakobsen F, Mogensen CE (1981) The use of HPLC to elucidate the metabolism and urinary excretion of furosemide and its metabolic products. Acta Pharmacol Toxicol 49: 223–229Google Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • M. M. Hammarlund
    • 1
  • L. K. Paalzow
    • 1
  • B. Odlind
    • 2
  1. 1.Department of Biopharmaceutics and PharmacokineticsUniversity of UppsalaUppsalaSweden
  2. 2.Department of Internal MedicineUniversity HospitalUppsalaSweden

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