Clinical pharmacology of exogenously administered alkaline phosphatase.

P. Pickkers; F. Snellen; P. Rogiers; J. Bakker; P. Jorens; J. Meulenbelt; H. Spapen; J.E. Tulleken; R. Lins; S. Ramael; M. Bulitta; J.G. van der Hoeven

Clinical pharmacology of exogenously administered alkaline phosphatase.

P. Pickkers, F. Snellen, P. Rogiers, J. Bakker, P. Jorens, J. Meulenbelt, H. Spapen, J.E. Tulleken, R. Lins, S. Ramael, M. Bulitta, J.G. van der Hoeven

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

PURPOSE: To evaluate the clinical pharmacology of exogenous alkaline phosphatase (AP). METHODS: Randomized, double-blind, placebo-controlled sequential protocols of (1) ascending doses and infusion duration (volunteers) and (2) fixed dose and duration (patients) were conducted at clinical pharmacology and intensive care units. A total of 103 subjects (67 male volunteers and 36 patients with severe sepsis) were administered exogenous, 10-min IV infusions (three ascending doses) or 24-72 h continuous (132.5-200 U kg(-1) 24 h(-1)) IV infusion with/without preceding loading dose and experimental endotoxemia for evaluations of pharmacokinetics, pharmacodynamics, safety parameters, antigenicity, inflammatory markers, and outcomes. RESULTS: Linearity and dose-proportionality were shown during 10-min infusions. The relatively short elimination half-life necessitated a loading dose to achieve stable enzyme levels. Pharmacokinetic parameters in volunteers and patients were similar. Innate immunity response was not significantly influenced by AP, while renal function significantly improved in sepsis patients. CONCLUSIONS: The pharmacokinetics of exogenous AP is linear, dose-proportional, exhibit a short half-life, and are not influenced by renal impairment or dialysis.

Original language	Undefined/Unknown
Pages (from-to)	393-402
Number of pages	9
Journal	European Journal of Clinical Pharmacology
Volume	65
Issue number	4
Publication status	Published - 2009

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Pickkers-Eur J Clin Pharmacol 2009 65 393-402
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Cite this

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title = "Clinical pharmacology of exogenously administered alkaline phosphatase.",

abstract = "PURPOSE: To evaluate the clinical pharmacology of exogenous alkaline phosphatase (AP). METHODS: Randomized, double-blind, placebo-controlled sequential protocols of (1) ascending doses and infusion duration (volunteers) and (2) fixed dose and duration (patients) were conducted at clinical pharmacology and intensive care units. A total of 103 subjects (67 male volunteers and 36 patients with severe sepsis) were administered exogenous, 10-min IV infusions (three ascending doses) or 24-72 h continuous (132.5-200 U kg(-1) 24 h(-1)) IV infusion with/without preceding loading dose and experimental endotoxemia for evaluations of pharmacokinetics, pharmacodynamics, safety parameters, antigenicity, inflammatory markers, and outcomes. RESULTS: Linearity and dose-proportionality were shown during 10-min infusions. The relatively short elimination half-life necessitated a loading dose to achieve stable enzyme levels. Pharmacokinetic parameters in volunteers and patients were similar. Innate immunity response was not significantly influenced by AP, while renal function significantly improved in sepsis patients. CONCLUSIONS: The pharmacokinetics of exogenous AP is linear, dose-proportional, exhibit a short half-life, and are not influenced by renal impairment or dialysis.",

author = "P. Pickkers and F. Snellen and P. Rogiers and J. Bakker and P. Jorens and J. Meulenbelt and H. Spapen and J.E. Tulleken and R. Lins and S. Ramael and M. Bulitta and {van der Hoeven}, J.G.",

year = "2009",

language = "Undefined/Unknown",

volume = "65",

pages = "393--402",

journal = "European Journal of Clinical Pharmacology",

issn = "0031-6970",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "4",

}

TY - JOUR

T1 - Clinical pharmacology of exogenously administered alkaline phosphatase.

AU - Pickkers, P.

AU - Snellen, F.

AU - Rogiers, P.

AU - Bakker, J.

AU - Jorens, P.

AU - Meulenbelt, J.

AU - Spapen, H.

AU - Tulleken, J.E.

AU - Lins, R.

AU - Ramael, S.

AU - Bulitta, M.

AU - van der Hoeven, J.G.

PY - 2009

Y1 - 2009

N2 - PURPOSE: To evaluate the clinical pharmacology of exogenous alkaline phosphatase (AP). METHODS: Randomized, double-blind, placebo-controlled sequential protocols of (1) ascending doses and infusion duration (volunteers) and (2) fixed dose and duration (patients) were conducted at clinical pharmacology and intensive care units. A total of 103 subjects (67 male volunteers and 36 patients with severe sepsis) were administered exogenous, 10-min IV infusions (three ascending doses) or 24-72 h continuous (132.5-200 U kg(-1) 24 h(-1)) IV infusion with/without preceding loading dose and experimental endotoxemia for evaluations of pharmacokinetics, pharmacodynamics, safety parameters, antigenicity, inflammatory markers, and outcomes. RESULTS: Linearity and dose-proportionality were shown during 10-min infusions. The relatively short elimination half-life necessitated a loading dose to achieve stable enzyme levels. Pharmacokinetic parameters in volunteers and patients were similar. Innate immunity response was not significantly influenced by AP, while renal function significantly improved in sepsis patients. CONCLUSIONS: The pharmacokinetics of exogenous AP is linear, dose-proportional, exhibit a short half-life, and are not influenced by renal impairment or dialysis.

AB - PURPOSE: To evaluate the clinical pharmacology of exogenous alkaline phosphatase (AP). METHODS: Randomized, double-blind, placebo-controlled sequential protocols of (1) ascending doses and infusion duration (volunteers) and (2) fixed dose and duration (patients) were conducted at clinical pharmacology and intensive care units. A total of 103 subjects (67 male volunteers and 36 patients with severe sepsis) were administered exogenous, 10-min IV infusions (three ascending doses) or 24-72 h continuous (132.5-200 U kg(-1) 24 h(-1)) IV infusion with/without preceding loading dose and experimental endotoxemia for evaluations of pharmacokinetics, pharmacodynamics, safety parameters, antigenicity, inflammatory markers, and outcomes. RESULTS: Linearity and dose-proportionality were shown during 10-min infusions. The relatively short elimination half-life necessitated a loading dose to achieve stable enzyme levels. Pharmacokinetic parameters in volunteers and patients were similar. Innate immunity response was not significantly influenced by AP, while renal function significantly improved in sepsis patients. CONCLUSIONS: The pharmacokinetics of exogenous AP is linear, dose-proportional, exhibit a short half-life, and are not influenced by renal impairment or dialysis.

M3 - Article

SN - 0031-6970

VL - 65

SP - 393

EP - 402

JO - European Journal of Clinical Pharmacology

JF - European Journal of Clinical Pharmacology

IS - 4

ER -