Skip to main content
SpringerLink
Log in

Penetration of ceftazidime into human pancreas

Penetration von Ceftazidim in das Pankreas beim Menschen

  • Originalia
  • Published:
Infection Aims and scope Submit manuscript

Summary

The use of antibiotics in patients with severe acute pancreatitis (stage II and III) is indicated since bacterial complications are the most common cause of death in these patients. In the present study the penetration of ceftazidime into pancreatic juice, into healthy and chronically inflamed pancreatic tissue as well as into necrotic regions in cases of severe acute pancreatitis was investigated. A peak concentration of 12.9±5.9 mg/l was found 60 min after intravenous administration of 35 mg/kg of the drug, which is 32% of the corresponding serum levels. Pancreatic tissue concentrations varied between 9 and 79% of the corresponding serum levels, depending on the stage of inflammation. After five days of antibiotic treatment with doses of 2 g t.i.d., concentrations between 1.8 and 6.9 mg/kg were detected even in pancreatic necroses. This suggests that sufficient antibacterial levels of ceftazidime were present in all pancreatic compartments analyzed following administration of common therapeutic dosages. Therefore, from a pharmacokinetic point of view, ceftazidime could be a potentially effective drug for the treatment of pancreatitis.

Zusammenfassung

Der Einsatz von Antibiotika bei schwerer akuter Pankreatitis (Stadium II und III) ist indiziert, da bakterielle Komplikationen häufigste Todesursache sind. Ceftazidim wurde hinsichtlich seiner Permeation in das Pankreassekret, in gesundes und chronisch entzündetes Pankreasgewebe sowie in nekrotische Areale bei schwerer Pankreatitis des Menschen untersucht. Im Pankreassekret fand sich 60 Minuten nach intravenöser Gabe von 35 mg/kg eine Spitzenkonzentration von 12,9±5,9 mg/l. Das sind 32% des korrespondierenden Serumspiegels. Die Gewebespiegel variierten, in Abhängigkeit vom Enzündungsstadium, zwischen 9 und 79% der jeweiligen Serumkonzentration. Auch in Pankreasnekrosen ließen sich nach fünftägiger Behandlung (3 × 2 g) Ceftazidimspiegel zwischen 1,8 und 6,9 mg/kg nachweisen. Somit sind in allen untersuchten Kompartimenten ausreichend hohe, antibakterielle Wirkspiegel nach Gabe von Ceftazidim in therapeutischer Dosierung nachweisbar, so daß sich aus pharmakokinetischer Sicht Ceftazidim als ein potentiell geeignetes Präparat bei Pankreatitis anbietet.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Beger, H. G., Bittner, R., Block, S. Bacterial contamination of pancreatic necrosis. Gastroenterology 91 (1986) 433–438.

    Google Scholar 

  2. Lumbsen, A., Bradley, E. L. Secondary pancreatic infections. Surgery 170 (1990) 459–467.

    Google Scholar 

  3. Bradley, E. L. Antibiotics in acute pancreatitis. Current status and further directions. Am. J. Surg. 158 (1989) 472–477.

    Google Scholar 

  4. Frey, C. F., Bradley, E. L., Beger, H. G. Progress in acute pancreatitis. Surg. Gynecol. Obstet. 167 (1988) 282–286.

    Google Scholar 

  5. Bittner, R., Block, S., Büchler, M., Beger, H. G. Pancreatic abscess and infected pancreatic necrosis. Different local septic complications in acute pancreatitis. Dig. Dis. Sci. 32 (1987) 1082–1987.

    Google Scholar 

  6. Craig, R. M., Dordal, E., Myles, L. The use of ampicillin in acute pancreatitis. Ann. Intern. Med. 83 (1975) 831–832.

    Google Scholar 

  7. Howes, R., Zuidema, G. D., Cameron, J. E. Evaluation of prophylactic antibiotics in acute pancreatitis. Surg. Res. 18 (1975) 197–200.

    Google Scholar 

  8. Finch, W. T., Sawyers, J. L., Schenker, S. A prospective study to determine the efficacy of antibiotics in acute pancreatitis. Ann. Surg. 183 (1976) 667–671.

    Google Scholar 

  9. Büchler, M., Malfertheiner, P., Frieß, H., Bittner, R., Vanek, E., Schlegel, P., Beger, H. G. The penetration of antibiotics into human pancreas. Infection 17 (1989) 20–25.

    Google Scholar 

  10. Koch, K., Drewelow, B., Liebe, S., Reding, R., Riethling, A. K. Die Pankreasgängigkeit von Antibiotika. Chirurg 62 (1991) 317–332.

    Google Scholar 

  11. Bradley, E. L. Management of infected pancreatic necrosis by open drainage. Ann. Surg. 296 (1987) 542–550.

    Google Scholar 

  12. Drewelow, B., Koch, K.: Untersuchungen zur Pharmakokinetik von Antibiotika im Pankreas. Habilitationsschrift. Med. Fak., Universität Rostock, 1989.

  13. Reding, R. Pankreasanastomosen. Chirurg 59 (1988) 820–827.

    Google Scholar 

  14. Klempa, I., Baca, I., Menzel, J., Schuszdierra, V. Auswirkungen von Somatostatin auf die basale und stimulierte exokrine Pankreassekretion nach partieller Duodenopancreatektomie. Eine experimentelle Studie. Chirurg 62 (1991) 293–299.

    Google Scholar 

  15. Kavanagh, F. Antibiotic assay — principles and precautions. In:Hash, J. H. (ed.): Methods in enzymology. Vol. XLIII, Antibiotics. Academic Press, New York 1975, pp. 55–69.

    Google Scholar 

  16. Otto, C.: Vergleichende Untersuchungen zur Pharmakokinetik von Ceftazidim im Pankreas bei Ratte, Hund und Mensch. Promotionsschrift, Med. Fak., Universität Rostock, 1993.

  17. Drewelow, B., Koch, K. Zur Pharmakokinetik von Ampicillin in der Bauchspeicheldrüse. Wiss. z. Univ. Rostock N-Reihe 9 (1988) 85–89.

    Google Scholar 

  18. Roberts, W. A., Williams, R. J. Ampicillin concentrations in pancreatic fluid obtained at endoscopic retrograde cholangiopancreatography (ERCP). Scand. J. Gastroenterol. 14 (1979) 669–672.

    Google Scholar 

  19. Burns, G. P., Stein, E. A., Kabnik, L. S. Blood-pancreatic juice barrier to antibiotic excretion. Am. J. Surg. 151 (1986) 205–208.

    Google Scholar 

  20. Gregg, J. A., Maher, L., DeGirolami, P. C.: Secretion of β-lactam antibiotics in pure human pancreatic juice. Am. J. Surg. (1985) 333–335.

  21. Wallace, J., Cushing, R., Bawdon, R., Sugawa, C. Antibiotic levels in human pancreatic juice. Surg. Forum 34 (1983) 147–148.

    Google Scholar 

  22. Drewelow, B., Koch, K., Liebe, S. Untersuchungen von Pharmakokinetik von Antibiotika im Pankreas. Med.-Rep. 18 (1989) 604–609.

    Google Scholar 

  23. Benveniste, G. L., Morris, R. G. Penetration of cefotaxime into pancreatic juice. Lancet i (1985) 588–589.

    Google Scholar 

  24. Brattström, G., Tyden, G., Malmborg, A. S. Studies of exocrine secretion of segmental pancreatic grafts with special reference to the diagnosis of rejection and to the penetration of drugs into the pancreatic juice. Transplant. Proc. 19 (1987) 2332–2335.

    Google Scholar 

  25. Brattström, G., Malmborg, A. S., Tyden, G. Penetration of clindamycin, cefoxitin, and piperacillin into pancreatic juice of man. Surgery 103 (1988) 563–567.

    Google Scholar 

  26. Drewelow, B., Koch, K., Stumper, S., Liebe, S., Stumper, C., Kinast, R., Merkel, G., Riethling, A. K. Factors determining the penetration of antibiotics into the pancreas. Zentrlbl. Pharm. 129 (1990) 307–310.

    Google Scholar 

  27. Pederzoli, P., Falconi, M., Martini, N., Cevallini, G., Bassi, C., Orcalli, F. Rifampicin and ceftazidime concentrations in pure pancreatic juice. Dig. Dis. Sci. 30 (1985) 985.

    Google Scholar 

  28. Walstad, R. A., Wiig, J. N., Thurmann-Nielsen, E., Halvorsen, T. B. Die Pharmakokinetik von Ceftazidim bei Patienten mit Gallenwegserkrankungen. Europ. J. Clin. Pharmacol. 31 (1986) 327–331.

    Google Scholar 

  29. Rethel, R., Hoffmann, U., Hoffmeister, A. W., Seyfried, J., Wagner, L., Walker, G., Weiss, H., Willig, H. Zur Pankreasgängigkeit von Sulfamethoxazol und Trimethoprim. Med. Welt 31 (1980) 991–994.

    Google Scholar 

  30. Koch, K., Drewelow, B., Liebe, S. Die Penetration von Cefotiam in das Pankreas des Menschen. Wiss. z. Univ. Rostock, N-Reihe 12 (1991) 27–33.

    Google Scholar 

  31. Friess, H., Büchler, M., Malfertheiner, P., Isenmann, R., Schlegel, P., Beger, H. G.: Concentrations of different bactericidal antibiotics in human pancreatic tissue. XXI Meeting of the European Pancreatic Club, 1989.

  32. Wilkins, T. D., West, S. H. E. Therapy of anaerobic infections. Infection 11 (1983) (Suppl. 2) S105-S109.

    Google Scholar 

  33. Brown, R. F., Kinnick, M. D., Morin, J. M., Vasileff, R. T., Counter, F. T., Davidson, E. O., Ensminger, P. W., Eudaly, J. A., Kasher, J. S., Katner, A. S., Koehler, R. E., Kurz, K. D., Lindstrom, T. D., Lunn, W. H. W., Preston, D. A., Ott, J. L., Quay, J. F., Shadle, J. K., Steinberg, M. I., Stucky, J. F., Swartzendruber, J. K., Turner, J. R., Webber, J. A., Wright, W. E., Zimmerman, K. M. Synthesis and biological evaluation of a series of parenteral 3′-quarternary ammonium cephalosporins. J. Med. Chem. 33 (1990) 2114–2121.

    Google Scholar 

  34. Neu, H. C. Relation of structural properties of β-lactam antibiotics to antibacterial activity. Am. J. Med. 79 (1985) (Suppl. 2A) 2–13.

    Google Scholar 

  35. Meulemans, A., Vicard, P., Mohler, J., Vulpillat, M. Determination of antibiotic lipophilicity with a micromethod: application to brain permeability in man and rats. Chemotherapy 34 (1988) 90–95.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Pharmakologie und Toxikologie, Universität Rostock, Schillingallee 70, D-18055, Rostock

    B. Drewelow,  Christina Otto &  Anne-Kathrin Riethling

  2. Universität Rostock, Schilling Allee 35, D-18055, Rostock, Germany

    K. Koch &  A. Franke

Authors
  1. B. Drewelow
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christina Otto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anne-Kathrin Riethling
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. Koch
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Franke
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Drewelow, B., Otto, C., Riethling, AK. et al. Penetration of ceftazidime into human pancreas. Infection 21, 229–234 (1993). https://doi.org/10.1007/BF01728896

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01728896

Keywords

Search

Navigation