Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Rectal pharmacokinetics of budesonide


The pharmacokinetics and systemic availability of budesonide after rectal administration of two single enema doses (2 mg in 100 ml fluid of almost identical composition) were compared in 15 healthy volunteers. In 11 of these subjects, 2 mg oral budesonide in a gelatine capsule was given on a separate occasion. An intravenous administration (0.5 mg) was given as reference. With this design, individual hepatic bypass of the rectally administered budesonide dose could be estimated. The pharmacokinetics of the two enema formulations were similar, although not bioequivalent. Mean systemic availability was 16% (range 4.2–43%) and 15% (3.2–50%) after rectal administration and 6.3% (2.4–10%) after oral administration. The rectal data revealed a small intra- but a substantial inter-subject variability in systemic availability. Cmax was 3.3 nmol·l-1 (0.95–8.2), 3.0 nmol·l-1 (0.64–8.9) and 1.3 nmol·l-1 (0.61–3.0), respectively, for the three formulations. Absorption was rapid and essentially terminated within 3 h after rectal dosing [tmax=1.3 h for both formulations (range 0.5–2.0)], but was slower after oral dosing [tmax=2.1 h (1.0–6.0)]. If a complete absorption after oral and rectal dosing is assumed, the fraction of the rectal dose entering the liver at first pass can be calculated to be 88% (55–99%).

The higher systemic availability and intersubject variability after rectal dosing does not seem to be caused by differences in first-pass liver metabolism but rather by hepatic bypass of a varying portion of administered drug. This portion seems to be typical for an individual and might be explained by anatomical differences between subjects.

This is a preview of subscription content, log in to check access.


  1. 1.

    Danielsson Å, Löfberg R, Persson T, et al (1992) A steroid enema, budesonide, lacking systemic effects for the treatment of distal ulcerative colitis or proctitis. Scand J Gastroenterol 27:9–12.

  2. 2.

    Danielsson Å, Hellers G, Lyrenäs E, et al (1987) A controlled randomized trial of budesonide versus prednisolone retention enemas in active distal ulcerative colitis. Scand J Gastroenterol 22:987–992.

  3. 3.

    Löfberg R, Östergaard Thomsen O, Langholtz E, et al (1994) Budesonide versus prednisolone retention enemas in active distal ulcerative colitis. Aliment Pharmacol Ther 8:623–629.

  4. 4.

    Ryrfeldt Å, Andersson P, Edsbäcker S, Tönnesson M, Davies D, Pauwles R (1982) Pharmacokinetics and metabolism of budesonide, a selective glucocorticoid. Eur J Respir Dis 63 [Suppl 11]:86–95.

  5. 5.

    De Boer AG, Breimer DD, Mattie H, Pronk J, Gubbens-Stibbe JM (1979) Rectal bioavailability of lidocaine in man: partial avoidance of “first pass” metabolism. Clin Pharmacol Ther 26:702–709.

  6. 6.

    Garg DC, Wagner JG, Sakmar E, Weidler DJ, Albert KS (1979) Rectal and oral absorption of methylprednisolone acetate. Clin Pharmacol Ther 26:232–239.

  7. 7.

    Möllmann H, Barth J, Möllmann C, Tunn S, Krieg M, Derendorf H (1991) Pharmacokinetics and rectal bioavailability of hydrocortisone acetate. J Pharm Sci 80:835–836.

  8. 8.

    De Boer AG, Moonelaar F, de Leede LGJ, Breimer DD (1982) Rectal drug administration: clinical pharmacokinetic considerations. Clin Pharmacokinet 7:285–311.

  9. 9.

    Lindberg C, Blomquist A, Paulson J (1992) Determination of (22R,S)budesonide in human plasma by automated liquid chromatography/thermospray mass spectrometry. Biol Mass Spectrom 21:525–533.

  10. 10.

    Rowland M, Tozer T (1989) Clinical pharmacokinetics. Lea and Febiger, Philadelphia.

  11. 11.

    Vaughan DP, Dennis M (1978) Mathematical basis of point-area deconvolution method for determining in vivo input function. J Pharm Sci 67:663–665.

  12. 12.

    US Food and Drug Administration (1992) Guidance on statistical procedures for bioequivalence studies using a standard two-treatment cross-over design, July 1992. The Division of Bioequivalence, Office of Generic Drugs, US Food and Drug Administration, Rockville, MD.

  13. 13.

    Chow S-H, Liu J-P (1994) Recent statistical developments in bioequivalence trials — a review of the FDA guidance. Drug Informat J 28:851–864.

  14. 14.

    Ryrfeldt Å, Edsbäcker S, Andersson KE (1985) Fate and effects of [3H]budesonide in man after intravenous and nasal administration of the drug. Eur J Clin Pharmacol 29:477–481.

  15. 15.

    Thorsson L, Edsbäcker S, Conradsson T-B (1994) Lung deposition of budesonide from Turbuhaler® is twice that from a pressurized metered-dose inhaler P-MDI. Eur Respir J 7:1839–1844.

  16. 16.

    Gustavsson LE, Benet LZ (1986) Pharmacokinetics of natural and synthetic glucocorticoids. In: Anderson DC, Winter JSD (eds) Adrenal cortex. Butterworths, London, pp 235–281.

  17. 17.

    Nilsson M, Edsbäcker S, Larsson P, Wirén JE (1994) Dose-proportional kinetics of budesonide controlled ileal release (CIR) capsules. Abstr. World Congress Gastroenterology, Los Angeles 1994 (Poster No 1783).

  18. 18.

    De Leede LGJ, deBoer AG, Feijen CD, Breimer DD (1984) Site specific rectal drug administration in man with an osmotic system: influence on “first-pass” elimination of lidocaine. Pharm Res 1:129–134.

  19. 19.

    Nyman-Pantelidis M, Nilsson Å, Wagner Z, Borg» O (1994) Pharmacokinetics and retrograde spread of budesonide enemas in patients with distal ulcerative colitis. Aliment Pharmacol Ther 8:617–622.

Download references

Author information

Correspondence to K. Dahlström.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Dahlström, K., Edsbäcker, S. & Källén, A. Rectal pharmacokinetics of budesonide. Eur J Clin Pharmacol 49, 293–298 (1996).

Download citation

Key words

  • Budesonide
  • enema
  • pharmacokinetics
  • healthy subjects
  • hepatic bypass