European Journal of Clinical Pharmacology

, Volume 41, Issue 1, pp 11–16

The assessment of the systemic effects of inhaled glucocorticosteroids

The effects of inhaled budesonide vs oral prednisolone on calcium metabolism
  • B. H. Jennings
  • K.-E. Andersson
  • S.-Å. Johansson
Originals

Summary

In a randomized, double-blind crossover study, the effects of 0.8, 1.6 and 3.2 mg/day inhaled budesonide and 5, 10 and 20 mg/day oral prednisolone on mineral metabolism were compared. Twelve healthy subjects (4 m, 8 f) were treated for 1 week at each dosage level, the graduated dosages being given in ascending order. Budesonide and prednisolone were given twice daily and once daily, respectively, which reflects the schedules common in clinical practice.

Serum calcium and the regulatory hormones of calcium metabolism (parathyroid hormone, vitamin D metabolites and calcitonin) were not changed either by prednisolone or budesonide. Prednisolone significantly increased 24 h and 08.00 h fasting urinary calcium excretion and decreased renal calcium reabsorption, while budesonide had little or no effect on urinary calcium loss and increased renal reabsorption at the highest dose level. Both drugs significantly increased renal phosphate reabsorption and serum phosphate levels, but prednisolone caused greater increases than budesonide.

In conclusion, during short-term treatment with the dosages used, inhaled budesonide had less effect on calcium and phosphate metabolism than oral prednisolone, and so it may have a lesser action on the skeleton of the type contributing to osteoporosis during long-term treatment.

Key words

Budesonide Prednisolone calcium phosphate healthy volunteers osteoporosis mineral metabolism 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Hahn TJ, Halstead LR, Teitelbaum SL, Hahn BH (1979) Altered mineral metabolism in glucocorticoid-induced osteopenia: Effect of 25(OH)D administration. J Clin Invest 64: 655–665Google Scholar
  2. 2.
    Hahn TJ, Halstead LR, Strates B, Imbimbo B, Baran DT (1980) Comparison of subacute effects of oxazacort and prednisone on mineral metabolism in man. Calcif Tiss Int 31: 109–115Google Scholar
  3. 3.
    Hahn TJ, Halstead LR, Baran DT (1981) Effects of short term glucocorticoid administration on intestinal calcium absorption and circulating vitamin D metabolite concentrations in man. J Clin Endocrinol Metab 52: 111–115Google Scholar
  4. 4.
    Dykman TR, Haralson KM, Gluck OS, Murphy WA, Teitelbaum SL, Hahn TJ, Hahn BH (1984) Effect of oral 1,25-dihydroxyvitamin D and calcium on glucocorticoid-induced osteopenia in patients with rheumatic diseases. Arth Rheum 27(12): 1336–1343Google Scholar
  5. 5.
    Laake H (1960) The action of corticosteroids on the renal reabsorption of calcium. Acta Endocrinol 34: 60–64Google Scholar
  6. 6.
    Caniggia A, Nuti R, Lore' F, Vattimo A (1981) Pathophysiology of the adverse effects of glucoactive corticosteroids on calcium metabolism in man. J Steroid Biochem 15: 153–161Google Scholar
  7. 7.
    Reid IR, Ibbertson HK (1987) Evidence for decreased tubular reabsorption of calcium in glucocorticoid-treated asthmatics. Horm Res 27: 200–204Google Scholar
  8. 8.
    Gennari C, Imbimbo B, Montagnani M, Bernini M, Nardi P, Avioli LV (1984) Effects of prednisolone and deflazacort on mineral metabolism and parathyroid hormone activity in humans. Calcif Tiss Int 36: 245–252Google Scholar
  9. 9.
    Suzuki Y, Ichikawa Y, Saito E, Homma M (1983) Importance of increased urinary excretion in the development of secondary hyperparathyroidism of patients under glucocorticoid therapy. Metabolism 32: 151–156Google Scholar
  10. 10.
    Fucik RF, Kukreja SC, Hargis GK, Bowser EN, Henderson WJ, Williams GA (1975) Effects of glucocorticoids on function of the parathyroid glands in man. J Clin Endocrinol Metab 40: 152–155Google Scholar
  11. 11.
    Seeman E, Kumar R, Hunder GC, Scott M, Heath III H, Riggs BL (1980) Production, degradation and circulating levels of 1,25 dihydroxyvitamin D in health and in chronic glucocorticoid excess. J Clin Invest 66: 664–669Google Scholar
  12. 12.
    Braun JJ, Juttmann JR, Visser TJ, Birkenhäger JC (1982) Short-term effect of prednisone on serum 1,25-dihydroxyvitamin D in normal individuals and in hyper- and hypoparathyroidism. Clin Endocrinol 17: 21–28Google Scholar
  13. 13.
    Toogood JH, Crilly RG, Jones G, Nadeau J, Wells GA (1988) Effect of high-dose inhaled budesonide on calcium and phosphate metabolism and the risk of osteoporosis. Am Rev Respir Dis 138: 57–61Google Scholar
  14. 14.
    Nordin BEC, Horsman A, Aaron J (1976) Diagnostic procedures. In Calcium, Phosphate and Magnesium Metabolism. Ed. BEC Nordin. Churchill LivingstoneGoogle Scholar
  15. 15.
    Fogh-Andersen N (1981) Ionized calcium analyzer with a builtin pH correction. Clin Chem 27(7): 1264–1267Google Scholar
  16. 16.
    von Knorring J, Slätis P, Weber TH, Helenius T (1982) Serum levels of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D and parathyroid hormone in patients with femoral neck fracture in southern Finland. Clin Endocrinol 17: 189–194Google Scholar
  17. 17.
    Reinhardt TA, Horst RL, Orf JW, Hollis BW (1984) A microassay for 1,25-dihydroxyvitamin D not requiring high performance liquid chromatography: Application to clinical studies. J Clin Endocrinol Metab 58: 91–98Google Scholar
  18. 18.
    Törnqvist K, Lamberg-Allardt C (1987) Systemic effects of 1,25-dihydroxyvitamin D3 on the pituitary-hypothalamic axis in rats. Acta Endocrinol 115: 225–228Google Scholar
  19. 19.
    Gilman AG (1972) Protein binding assays for cyclic nucleotides. Adv Cyclic Nucl Res 2: 9–24Google Scholar
  20. 20.
    Tovey KC, Oldham KG, Whelan JAM (1974) A simple direct assay for cyclic AMP in plasma and other biological samples using an improved competitive protein binding technique. Clin Chim Acta 56: 221–234Google Scholar
  21. 21.
    Toogood JH, Baskerville J, Jennings BH, Lefcoe NM, Johansson SÅ (1989) Bioequivalent doses of budesonide and prednisone in moderate and sever asthma. J Allergy Clin Immunol 84: 688–700Google Scholar
  22. 22.
    Johansson SÅ, Andersson KE, Brattsand R, Gruvstad E, Hedner P (1982) Topical and systemic glucocorticoid potencies of budesonide, beclomethasone dipropionate and prednisolone in man. Eur J Resp Dis 63 [Suppl 122]: 74–82Google Scholar
  23. 23.
    Jennings BH, Andersson KE, Johansson SÅ (1991) The assessment of systemic effects of inhaled glucocorticosteroids: A comparison of the effects of inhaled budesonide and oral prednisolone on adrenal function and markers of bone turnover. Eur J Clin Pharmacol 40: 77–82Google Scholar
  24. 24.
    Crilly RG, Nordin BEC (1982) Effect of corticosteroids on renal tubular reabsorption of calcium and phosphate. Calcif Tiss Int 34: 586Google Scholar
  25. 25.
    Reid IR (1989) Pathogenesis of treatment of steroid osteoporosis. Clin Endocrinol 30: 83–103Google Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • B. H. Jennings
    • 1
    • 2
  • K.-E. Andersson
    • 1
  • S.-Å. Johansson
    • 1
    • 2
  1. 1.Department of Clinical PharmacologyUniversity HospitalLundSweden
  2. 2.Department of Explorative Clinical ResearchClinical Pharmacology Section, AB DracoLundSweden

Personalised recommendations