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. 1992 Nov;36(11):2512–2517. doi: 10.1128/aac.36.11.2512

Increased oral bioavailability of ciprofloxacin in cystic fibrosis patients.

B A Christensson 1, I Nilsson-Ehle 1, B Ljungberg 1, A Lindblad 1, A S Malmborg 1, L Hjelte 1, B Strandvik 1
PMCID: PMC284363  PMID: 1489195

Abstract

The altered pharmacokinetic properties of, e.g., aminoglycosides in cystic fibrosis patients have to be considered when pulmonary exacerbations are treated. Since reported data on ciprofloxacin, a fluorinated quinolone, are conflicting, we compared intravenous and oral administration in cystic fibrosis patients when treating them for mild symptoms of pulmonary infection. All of the patients were colonized with Pseudomonas species. Ciprofloxacin was administered orally (15 mg/kg of body weight) or intravenously (6 mg/kg) twice a day for at least 10 days during separate treatment periods. Five healthy volunteers received single intravenous and oral doses. Pharmacokinetic evaluations were performed at first dose and at steady state. The results showed that cystic fibrosis patients have increased oral bioavailability of ciprofloxacin (80% in cystic fibrosis patients versus 57% in volunteers) and increased total clearance (688 ml/min in CF patients versus 528 ml/min in volunteers). Our data indicate that the pharmacokinetic properties of ciprofloxacin are altered in cystic fibrosis patients with mild symptoms of pulmonary exacerbations and that the changes most probably are due to cystic fibrosis per se or to the impact of chronic infection.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ARCHDEACON J. W., DANFORTH J. T., DUMMIT G. D. Factors affecting bile flow in the rabbit and rat. Am J Physiol. 1954 Sep;178(3):499–502. doi: 10.1152/ajplegacy.1954.178.3.499. [DOI] [PubMed] [Google Scholar]
  2. Alván G., Beermann B., Hjelte L., Lind M., Lindholm A., Strandvik B. Increased nonrenal clearance and increased diuretic efficiency of furosemide in cystic fibrosis. Clin Pharmacol Ther. 1988 Oct;44(4):436–441. doi: 10.1038/clpt.1988.177. [DOI] [PubMed] [Google Scholar]
  3. Ballard B. E. Pharmacokinetics and temperature. J Pharm Sci. 1974 Sep;63(9):1345–1358. doi: 10.1002/jps.2600630903. [DOI] [PubMed] [Google Scholar]
  4. Beresford C. H., Neale R. J., Brooks O. G. Iron absorption and pyrexia. Lancet. 1971 Mar 20;1(7699):568–572. doi: 10.1016/s0140-6736(71)91165-2. [DOI] [PubMed] [Google Scholar]
  5. Berg U., Kusoffsky E., Strandvik B. Renal function in cystic fibrosis with special reference to the renal sodium handling. Acta Paediatr Scand. 1982 Sep;71(5):833–838. doi: 10.1111/j.1651-2227.1982.tb09528.x. [DOI] [PubMed] [Google Scholar]
  6. Chang H. C. GASTRIC SECRETION IN FEVER AND INFECTIOUS DISEASES. J Clin Invest. 1933 Jan;12(1):155–169. doi: 10.1172/JCI100486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Davis R. L., Koup J. R., Williams-Warren J., Weber A., Heggen L., Stempel D., Smith A. L. Pharmacokinetics of ciprofloxacin in cystic fibrosis. Antimicrob Agents Chemother. 1987 Jun;31(6):915–919. doi: 10.1128/aac.31.6.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Drusano G. L. An overview of the pharmacology of intravenously administered ciprofloxacin. Am J Med. 1987 Apr 27;82(4A):339–345. [PubMed] [Google Scholar]
  9. Finkelstein E., Hall K. Aminoglycoside clearance in patients with cystic fibrosis. J Pediatr. 1979 Jan;94(1):163–164. doi: 10.1016/s0022-3476(79)80394-7. [DOI] [PubMed] [Google Scholar]
  10. Ganzinger U., Haslberger A. Pharmacokinetics of cephalosporins in normal and septicemic rabbits. Antimicrob Agents Chemother. 1985 Oct;28(4):473–477. doi: 10.1128/aac.28.4.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ganzinger U., Haslberger A., Schiel H., Omilian-Rosso R., Schütze E. Influence of endotoxin on the distribution of cephalosporins in rabbits. J Antimicrob Chemother. 1986 Jun;17(6):785–793. doi: 10.1093/jac/17.6.785. [DOI] [PubMed] [Google Scholar]
  12. Ghezzi P., Saccardo B., Villa P., Rossi V., Bianchi M., Dinarello C. A. Role of interleukin-1 in the depression of liver drug metabolism by endotoxin. Infect Immun. 1986 Dec;54(3):837–840. doi: 10.1128/iai.54.3.837-840.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goldfarb J., Stern R. C., Reed M. D., Yamashita T. S., Myers C. M., Blumer J. L. Ciprofloxacin monotherapy for acute pulmonary exacerbations of cystic fibrosis. Am J Med. 1987 Apr 27;82(4A):174–179. [PubMed] [Google Scholar]
  14. Guggenbichler J. P., Kienel G. Bioavailability of oral antibiotics in cystic fibrosis. Monogr Paediatr. 1979;10:34–40. [PubMed] [Google Scholar]
  15. Hedman A., Adan-Abdi Y., Alvan G., Strandvik B., Arvidsson A. Influence of the glomerular filtration rate on renal clearance of ceftazidime in cystic fibrosis. Clin Pharmacokinet. 1988 Jul;15(1):57–65. doi: 10.2165/00003088-198815010-00005. [DOI] [PubMed] [Google Scholar]
  16. Hedman A., Alván G., Strandvik B., Arvidsson A. Increased renal clearance of cefsulodin due to higher glomerular filtration rate in cystic fibrosis. Clin Pharmacokinet. 1990 Feb;18(2):168–175. doi: 10.2165/00003088-199018020-00006. [DOI] [PubMed] [Google Scholar]
  17. Hjelte L., Larsson M., Alvestrand A., Malmborg A. S., Strandvik B. Renal function in rats with essential fatty acid deficiency. Clin Sci (Lond) 1990 Oct;79(4):299–305. doi: 10.1042/cs0790299. [DOI] [PubMed] [Google Scholar]
  18. Hjelte L., Malmborg A. S., Strandvik B. Serum and sputum concentrations of netilmicin in combination with acylureidopenicillin and cephalosporins in clinical treatment of pulmonary exacerbations in cystic fibrosis. J Antimicrob Chemother. 1989 Jun;23(6):885–890. doi: 10.1093/jac/23.6.885. [DOI] [PubMed] [Google Scholar]
  19. Isles A., Spino M., Tabachnik E., Levison H., Thiessen J., MacLeod S. Theophylline disposition in cystic fibrosis. Am Rev Respir Dis. 1983 Apr;127(4):417–421. doi: 10.1164/arrd.1983.127.4.417. [DOI] [PubMed] [Google Scholar]
  20. Jacobs R. F., Trang J. M., Kearns G. L., Warren R. H., Brown A. L., Underwood F. L., Kluza R. B. Ticarcillin/clavulanic acid pharmacokinetics in children and young adults with cystic fibrosis. J Pediatr. 1985 Jun;106(6):1001–1007. doi: 10.1016/s0022-3476(85)80258-4. [DOI] [PubMed] [Google Scholar]
  21. Jusko W. J., Mosovich L. L., Gerbracht L. M., Mattar M. E., Yaffe S. J. Enhanced renal excretion of dicloxacillin in patients with cystic fibrosis. Pediatrics. 1975 Dec;56(6):1038–1044. [PubMed] [Google Scholar]
  22. KUO P. T., HUANG N. N., BASSETT D. R. The fatty acid composition of the serum chylomicrons and adipose tissue of children with cystic fibrosis of the pancreas. J Pediatr. 1962 Mar;60:394–403. doi: 10.1016/s0022-3476(62)80065-1. [DOI] [PubMed] [Google Scholar]
  23. Krutzén E., Bäck S. E., Nilsson-Ehle I., Nilsson-Ehle P. Plasma clearance of a new contrast agent, iohexol: a method for the assessment of glomerular filtration rate. J Lab Clin Med. 1984 Dec;104(6):955–961. [PubMed] [Google Scholar]
  24. Lavický J., Cerný J., Celeda L., Rotta J., Kvetina J., Raśková H., Kubícek A. Changes of pharmacokinetics of trimethoprim after pretreatment with streptococcal peptidoglycan. Eur J Drug Metab Pharmacokinet. 1986 Jan-Mar;11(1):17–22. doi: 10.1007/BF03189770. [DOI] [PubMed] [Google Scholar]
  25. LeBel M., Bergeron M. G., Vallée F., Fiset C., Chassé G., Bigonesse P., Rivard G. Pharmacokinetics and pharmacodynamics of ciprofloxacin in cystic fibrosis patients. Antimicrob Agents Chemother. 1986 Aug;30(2):260–266. doi: 10.1128/aac.30.2.260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ljungberg B., Nilsson-Ehle I. Advancing age and acute infection influence the kinetics of ceftazidime. Scand J Infect Dis. 1989;21(3):327–332. doi: 10.3109/00365548909035704. [DOI] [PubMed] [Google Scholar]
  27. Ljungberg B., Nilsson-Ehle I. Pharmacokinetics of ciprofloxacin in the elderly: increased oral bioavailability and reduced renal clearance. Eur J Clin Microbiol Infect Dis. 1989 Jun;8(6):515–520. doi: 10.1007/BF01967470. [DOI] [PubMed] [Google Scholar]
  28. Michalsen H., Bergan T. Pharmacokinetics of netilmicin in children with and without cystic fibrosis. Antimicrob Agents Chemother. 1981 Jun;19(6):1029–1031. doi: 10.1128/aac.19.6.1029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nahata M. C., Lubin A. H., Visconti J. A. Cephalexin pharmacokinetics in patients with cystic fibrosis. Dev Pharmacol Ther. 1984;7(4):221–228. doi: 10.1159/000457168. [DOI] [PubMed] [Google Scholar]
  30. Nilsson-Ehle I. Assay of ciprofloxacin and norfloxacin in serum and urine by high-performance liquid chromatography. J Chromatogr. 1987 Apr 24;416(1):207–211. doi: 10.1016/0378-4347(87)80504-2. [DOI] [PubMed] [Google Scholar]
  31. Pennington J. E., Dale D. C., Reynolds H. Y., MacLowry J. D. Gentamicin sulfate pharmacokinetics: lower levels of gentamicin in blood during fever. J Infect Dis. 1975 Sep;132(3):270–275. doi: 10.1093/infdis/132.3.270. [DOI] [PubMed] [Google Scholar]
  32. Reed M. D., Stern R. C., Bertino J. S., Jr, Myers C. M., Yamashita T. S., Blumer J. L. Dosing implications of rapid elimination of trimethoprim-sulfamethoxazole in patients with cystic fibrosis. J Pediatr. 1984 Feb;104(2):303–307. doi: 10.1016/s0022-3476(84)81019-7. [DOI] [PubMed] [Google Scholar]
  33. Rohwedder R., Bergan T., Thorsteinsson S. B., Scholl H. Transintestinal elimination of ciprofloxacin. Chemotherapy. 1990;36(2):77–84. doi: 10.1159/000238751. [DOI] [PubMed] [Google Scholar]
  34. Shapiro B. L., Lam L. F., Fast L. H. Premature senescence in cultured skin fibroblasts from subjects with cystic fibrosis. Science. 1979 Mar 23;203(4386):1251–1253. doi: 10.1126/science.424752. [DOI] [PubMed] [Google Scholar]
  35. Smith M. J., White L. O., Bowyer H., Willis J., Hodson M. E., Batten J. C. Pharmacokinetics and sputum penetration of ciprofloxacin in patients with cystic fibrosis. Antimicrob Agents Chemother. 1986 Oct;30(4):614–616. doi: 10.1128/aac.30.4.614. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Steen H. J., Scott E. M., Stevenson M. I., Black A. E., Redmond A. O., Collier P. S. Clinical and pharmacokinetic aspects of ciprofloxacin in the treatment of acute exacerbations of pseudomonas infection in cystic fibrosis patients. J Antimicrob Chemother. 1989 Nov;24(5):787–795. doi: 10.1093/jac/24.5.787. [DOI] [PubMed] [Google Scholar]
  37. Stenvinkel P., Hjelte L., Alván G., Hedman A., Hultman E., Strandvik B. Decreased renal clearance of sodium in cystic fibrosis. Acta Paediatr Scand. 1991 Feb;80(2):194–198. doi: 10.1111/j.1651-2227.1991.tb11833.x. [DOI] [PubMed] [Google Scholar]
  38. Strandvik B., Berg U., Kallner A., Kusoffsky E. Effect on renal function of essential fatty acid supplementation in cystic fibrosis. J Pediatr. 1989 Aug;115(2):242–250. doi: 10.1016/s0022-3476(89)80072-1. [DOI] [PubMed] [Google Scholar]
  39. Strandvik B., Hjelte L., Lindblad A., Ljungberg B., Malmborg A. S., Nilsson-Ehle I. Comparison of efficacy and tolerance of intravenously and orally administered ciprofloxacin in cystic fibrosis patients with acute exacerbations of lung infection. Scand J Infect Dis Suppl. 1989;60:84–88. [PubMed] [Google Scholar]
  40. Stutman H. R., Shalit I., Marks M. I., Greenwood R., Chartrand S. A., Hilman B. C. Pharmacokinetics of two dosage regimens of ciprofloxacin during a two-week therapeutic trial in patients with cystic fibrosis. Am J Med. 1987 Apr 27;82(4A):142–145. [PubMed] [Google Scholar]
  41. Sörgel F., Stephan U., Wiesemann H. G., Gottschalk B., Stehr C., Rey M., Böwing H. B., Dominick H. C., Geldmacher von Mallinckrodt M. High dose treatment with antibiotics in cystic fibrosis--a reappraisal with special reference to the pharmacokinetics of beta-lactams and new fluoroquinolones in adult CF-patients. Infection. 1987;15(5):385–396. doi: 10.1007/BF01647751. [DOI] [PubMed] [Google Scholar]
  42. Van Miert A. S., Van Gogh H., Wit J. G. The influence of pyrogen induced fever on absorption of sulpha drugs. Vet Rec. 1976 Dec 11;99(24):480–481. doi: 10.1136/vr.99.24.480. [DOI] [PubMed] [Google Scholar]
  43. Wise R., Donovan I. A. Tissue penetration and metabolism of ciprofloxacin. Am J Med. 1987 Apr 27;82(4A):103–107. [PubMed] [Google Scholar]
  44. Yaffe S. J., Gerbracht L. M., Mosovich L. L., Mattar M. E., Danish M., Jusko W. J. Pharmacokinetics of methicillin in patients with cystic fibrosis. J Infect Dis. 1977 May;135(5):828–831. doi: 10.1093/infdis/135.5.828. [DOI] [PubMed] [Google Scholar]
  45. de Groot R., Smith A. L. Antibiotic pharmacokinetics in cystic fibrosis. Differences and clinical significance. Clin Pharmacokinet. 1987 Oct;13(4):228–253. doi: 10.2165/00003088-198713040-00002. [DOI] [PubMed] [Google Scholar]
  46. di Sant'agnese P. A., Davis P. B. Cystic fibrosis in adults. 75 cases and a review of 232 cases in the literature. Am J Med. 1979 Jan;66(1):121–132. doi: 10.1016/0002-9343(79)90491-1. [DOI] [PubMed] [Google Scholar]

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