Title
Clinical pharmacology of exogenously administered alkaline phosphataseClinical pharmacology of exogenously administered alkaline phosphatase
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Research group
Laboratory Experimental Medicine and Pediatrics (LEMP)
Faculteit Geneeskunde
Publication type
article
Publication
Berlin,
Subject
Pharmacology. Therapy
Source (journal)
European journal of clinical pharmacology. - Berlin
Volume/pages
65(2009):4, p. 393-402
ISSN
0031-6970
ISI
000264176100008
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
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 2472 h continuous (132.5200 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.
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