Population pharmacokinetics of plasma-derived C1 esterase inhibitor concentrate used to treat acute hereditary angioedema attacks

Jonathan A. Bernstein, Bruce Ritchie, Robyn J. Levy, Richard L. Wasserman, Againdra K. Bewtra, David S. Hurewitz, Krystyna Obtulowicz, Avner Reshef, Dumitru Moldovan, Todor Shirov, Vesna Grivcheva-Panovska, Peter C. Kiessling, Fritz Schindel, Timothy J. Craig

Research output: Contribution to journalArticle

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Abstract

Background: C1 esterase inhibitor (C1-INH) replacement is recommended as a first-line therapy for acute edema attacks in hereditary angioedema (HAE). Only limited pharmacokinetic analyses of the administered C1-INH in plasma are available. Objective: To investigate retrospectively the population pharmacokinetics of a plasma-derived C1-INH (pC1-INH) concentrate used to treat acute HAE attacks in a randomized, placebo-controlled phase 2/3 study in patients with HAE. Methods: Acute abdominal and facial attacks were treated with either a pC1-INH concentrate (Berinert) at single intravenous doses of 10 or 20 U/kg body weight or placebo. Plasma sampling was conducted 0, 1, and 4 hours after dosing. A nonlinear retrospective population pharmacokinetic model was obtained using the assumption of a 1-compartment model. Results: The final population pharmacokinetic model was based on data from 97 patients treated with 10 or 20 U/kg of pC1-INH concentrate. The estimated mean half-life was 32.7 hours (90% confidence interval, 16.648.8 hours), and the estimated mean clearance was 0.92 mL/kg/h (90% confidence interval, 0.501.33 mL/kg/h). Conclusions: The half-life of the same pC1-INH concentrate reported in a previous study was confirmed by this retrospective population pharmacokinetic analysis in patients treated for acute HAE attacks. In contrast to other treatment options with shorter half-lives, the long half-life of pC1-INH concentrate may provide an extended period of protection, even after the symptoms of an attack have subsided.

Original languageEnglish
Pages (from-to)149-154
Number of pages6
JournalAnnals of Allergy, Asthma and Immunology
Volume105
Issue number2
DOIs
StatePublished - 2010

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Complement C1 Inhibitor Protein
Hereditary Angioedemas
Pharmacokinetics
Population
Half-Life
Placebos
Confidence Intervals
Edema
Body Weight

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Pulmonary and Respiratory Medicine
  • Medicine(all)

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Population pharmacokinetics of plasma-derived C1 esterase inhibitor concentrate used to treat acute hereditary angioedema attacks. / Bernstein, Jonathan A.; Ritchie, Bruce; Levy, Robyn J.; Wasserman, Richard L.; Bewtra, Againdra K.; Hurewitz, David S.; Obtulowicz, Krystyna; Reshef, Avner; Moldovan, Dumitru; Shirov, Todor; Grivcheva-Panovska, Vesna; Kiessling, Peter C.; Schindel, Fritz; Craig, Timothy J.

In: Annals of Allergy, Asthma and Immunology, Vol. 105, No. 2, 2010, p. 149-154.

Research output: Contribution to journalArticle

Bernstein, JA, Ritchie, B, Levy, RJ, Wasserman, RL, Bewtra, AK, Hurewitz, DS, Obtulowicz, K, Reshef, A, Moldovan, D, Shirov, T, Grivcheva-Panovska, V, Kiessling, PC, Schindel, F & Craig, TJ 2010, 'Population pharmacokinetics of plasma-derived C1 esterase inhibitor concentrate used to treat acute hereditary angioedema attacks', Annals of Allergy, Asthma and Immunology, vol. 105, no. 2, pp. 149-154. https://doi.org/10.1016/j.anai.2010.06.005
Bernstein, Jonathan A. ; Ritchie, Bruce ; Levy, Robyn J. ; Wasserman, Richard L. ; Bewtra, Againdra K. ; Hurewitz, David S. ; Obtulowicz, Krystyna ; Reshef, Avner ; Moldovan, Dumitru ; Shirov, Todor ; Grivcheva-Panovska, Vesna ; Kiessling, Peter C. ; Schindel, Fritz ; Craig, Timothy J. / Population pharmacokinetics of plasma-derived C1 esterase inhibitor concentrate used to treat acute hereditary angioedema attacks. In: Annals of Allergy, Asthma and Immunology. 2010 ; Vol. 105, No. 2. pp. 149-154.
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title = "Population pharmacokinetics of plasma-derived C1 esterase inhibitor concentrate used to treat acute hereditary angioedema attacks",
abstract = "Background: C1 esterase inhibitor (C1-INH) replacement is recommended as a first-line therapy for acute edema attacks in hereditary angioedema (HAE). Only limited pharmacokinetic analyses of the administered C1-INH in plasma are available. Objective: To investigate retrospectively the population pharmacokinetics of a plasma-derived C1-INH (pC1-INH) concentrate used to treat acute HAE attacks in a randomized, placebo-controlled phase 2/3 study in patients with HAE. Methods: Acute abdominal and facial attacks were treated with either a pC1-INH concentrate (Berinert) at single intravenous doses of 10 or 20 U/kg body weight or placebo. Plasma sampling was conducted 0, 1, and 4 hours after dosing. A nonlinear retrospective population pharmacokinetic model was obtained using the assumption of a 1-compartment model. Results: The final population pharmacokinetic model was based on data from 97 patients treated with 10 or 20 U/kg of pC1-INH concentrate. The estimated mean half-life was 32.7 hours (90{\%} confidence interval, 16.648.8 hours), and the estimated mean clearance was 0.92 mL/kg/h (90{\%} confidence interval, 0.501.33 mL/kg/h). Conclusions: The half-life of the same pC1-INH concentrate reported in a previous study was confirmed by this retrospective population pharmacokinetic analysis in patients treated for acute HAE attacks. In contrast to other treatment options with shorter half-lives, the long half-life of pC1-INH concentrate may provide an extended period of protection, even after the symptoms of an attack have subsided.",
author = "Bernstein, {Jonathan A.} and Bruce Ritchie and Levy, {Robyn J.} and Wasserman, {Richard L.} and Bewtra, {Againdra K.} and Hurewitz, {David S.} and Krystyna Obtulowicz and Avner Reshef and Dumitru Moldovan and Todor Shirov and Vesna Grivcheva-Panovska and Kiessling, {Peter C.} and Fritz Schindel and Craig, {Timothy J.}",
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T1 - Population pharmacokinetics of plasma-derived C1 esterase inhibitor concentrate used to treat acute hereditary angioedema attacks

AU - Bernstein, Jonathan A.

AU - Ritchie, Bruce

AU - Levy, Robyn J.

AU - Wasserman, Richard L.

AU - Bewtra, Againdra K.

AU - Hurewitz, David S.

AU - Obtulowicz, Krystyna

AU - Reshef, Avner

AU - Moldovan, Dumitru

AU - Shirov, Todor

AU - Grivcheva-Panovska, Vesna

AU - Kiessling, Peter C.

AU - Schindel, Fritz

AU - Craig, Timothy J.

PY - 2010

Y1 - 2010

N2 - Background: C1 esterase inhibitor (C1-INH) replacement is recommended as a first-line therapy for acute edema attacks in hereditary angioedema (HAE). Only limited pharmacokinetic analyses of the administered C1-INH in plasma are available. Objective: To investigate retrospectively the population pharmacokinetics of a plasma-derived C1-INH (pC1-INH) concentrate used to treat acute HAE attacks in a randomized, placebo-controlled phase 2/3 study in patients with HAE. Methods: Acute abdominal and facial attacks were treated with either a pC1-INH concentrate (Berinert) at single intravenous doses of 10 or 20 U/kg body weight or placebo. Plasma sampling was conducted 0, 1, and 4 hours after dosing. A nonlinear retrospective population pharmacokinetic model was obtained using the assumption of a 1-compartment model. Results: The final population pharmacokinetic model was based on data from 97 patients treated with 10 or 20 U/kg of pC1-INH concentrate. The estimated mean half-life was 32.7 hours (90% confidence interval, 16.648.8 hours), and the estimated mean clearance was 0.92 mL/kg/h (90% confidence interval, 0.501.33 mL/kg/h). Conclusions: The half-life of the same pC1-INH concentrate reported in a previous study was confirmed by this retrospective population pharmacokinetic analysis in patients treated for acute HAE attacks. In contrast to other treatment options with shorter half-lives, the long half-life of pC1-INH concentrate may provide an extended period of protection, even after the symptoms of an attack have subsided.

AB - Background: C1 esterase inhibitor (C1-INH) replacement is recommended as a first-line therapy for acute edema attacks in hereditary angioedema (HAE). Only limited pharmacokinetic analyses of the administered C1-INH in plasma are available. Objective: To investigate retrospectively the population pharmacokinetics of a plasma-derived C1-INH (pC1-INH) concentrate used to treat acute HAE attacks in a randomized, placebo-controlled phase 2/3 study in patients with HAE. Methods: Acute abdominal and facial attacks were treated with either a pC1-INH concentrate (Berinert) at single intravenous doses of 10 or 20 U/kg body weight or placebo. Plasma sampling was conducted 0, 1, and 4 hours after dosing. A nonlinear retrospective population pharmacokinetic model was obtained using the assumption of a 1-compartment model. Results: The final population pharmacokinetic model was based on data from 97 patients treated with 10 or 20 U/kg of pC1-INH concentrate. The estimated mean half-life was 32.7 hours (90% confidence interval, 16.648.8 hours), and the estimated mean clearance was 0.92 mL/kg/h (90% confidence interval, 0.501.33 mL/kg/h). Conclusions: The half-life of the same pC1-INH concentrate reported in a previous study was confirmed by this retrospective population pharmacokinetic analysis in patients treated for acute HAE attacks. In contrast to other treatment options with shorter half-lives, the long half-life of pC1-INH concentrate may provide an extended period of protection, even after the symptoms of an attack have subsided.

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