Skip to content

Advertisement

  • Poster presentation
  • Open Access

Pharmacokinetic–pharmacodynamic analysis of human purified C1-esterase inhibitor in patients with sepsis

  • 1,
  • 1 and
  • 1
Critical Care200812 (Suppl 2) :P382

https://doi.org/10.1186/cc6603

  • Published:

Keywords

  • Inflammatory Response
  • Emergency Medicine
  • Total Dosage
  • Intravenous Infusion
  • Inverse Correlation

Introduction

Several randomized prospective studies showed some beneficial protective effects of exogenous human purified C1-esterase inhibitor (C1INH) in patients with sepsis [1, 2]. Our purpose was to evaluate influence of systemic inflammation on the pharmacokinetic–pharmacodynamic of C1INH in patients with sepsis.

Methods

C1INH (Bicizar®; BioGenius LLC, Russia) was administered at the total dosage of 12,000 U in 48 hours (scheme of infusion: 6,000 U, 3,000 U, 2,000 U, 1,000 U every 12 hours) to 13 patients meeting ACCP/SCCM sepsis criteria during the first 24 hours after hospitalization. C1INH activity and C3, C4, IL-6 and procalcitonin levels were measured at baseline, 5 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours and 10 hours after C1INH intravenous infusion. The ratio of Cinitial to Cmax 0–10 hours reflected changes in C1INH activity after 6,000 U infusion. AUC 0–10 hours was calculated after correction of the C1INH activity–time curve to baseline.

Results

The median C1INH maximal shift after the first infusion was 55% (38–75%), as reflected by Cinitial/Cmax 0–10 hours. The calculated AUC 0–10 hours was 8.8 U-hours/ml (4.6–14.5 U-hours/ml). In patients with lower Cinitial 1.69 U/ml (0.96–2.65 U/ml), levels of C3 (r = 0.69, P < 0.01) and C4 (r = 0.67, P < 0.05) at baseline were likely to be decreased. A direct correlation between C3 level and Cinitial/Cmax 0–10 hours (r = 0.49, P < 0.05) as well as inverse correlation with AUC 0–10 hours (r = -0.613, P < 0.05) were found. The significant correlation of Cinitial/Cmax 0–10 hours with the baseline procalcitonin was also observed (r = 0.57, P < 0.05).

Conclusion

The shift in C1INH activity after 6,000 U infusion of purified protein was likely to be connected with baseline compliment activity in sepsis. Initial C3 and C4 depletion was associated with increased C1INH activity. The pharmacokinetic–pharmacodynamic profile of human purified C1INH might also be influenced by the severity of systemic inflammatory response. These factors could have some implication in the dosage-adjustment strategy.

Authors’ Affiliations

(1)
Sechenov Medical Academy, Moscow, Russian Federation.

References

  1. Caliezi C, et al.: Crit Care Med. 2002, 30: 1722-1728. 10.1097/00003246-200208000-00008PubMedView ArticleGoogle Scholar
  2. Zeerleder S, et al.: Clin Diagn Lab Immunol. 2003, 10: 529-535. 10.1128/CDLI.10.4.529-535.2003PubMedPubMed CentralGoogle Scholar

Copyright

© BioMed Central Ltd 2008

This article is published under license to BioMed Central Ltd.

Advertisement