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Clinical pharmacology of exogenously administered alkaline phosphatase
- Source :
- European Journal of Clinical Pharmacology, 65(4), 393-402. Springer Verlag, European Journal of Clinical Pharmacology, 65, 4, pp. 393-402, European Journal of Clinical Pharmacology, European Journal of Clinical Pharmacology, Springer Verlag, 2008, 65 (4), pp.393-402. ⟨10.1007/s00228-008-0591-6⟩, European Journal of Clinical Pharmacology, 65, 393-402, European journal of clinical pharmacology
- Publication Year :
- 2009
-
Abstract
- Contains fulltext : 79632.pdf (Publisher’s version ) (Closed access) 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.
- Subjects :
- Adult
Male
EXPRESSION
medicine.medical_specialty
Renal failure
Time Factors
Pharmacology
Loading dose
law.invention
Sepsis
Pharmacokinetics
Double-Blind Method
law
PHOSPHODIESTERASE ACTIVITY
Internal medicine
Intensive care
Alkaline phosphatase
medicine
Humans
Pharmacology (medical)
Infusions, Intravenous
Volunteer
ComputingMilieux_MISCELLANEOUS
Aged
Inflammation
Clinical pharmacology
SEPSIS
business.industry
Tumor Necrosis Factor-alpha
Pharmacology. Therapy
Interleukins
SEPTIC SHOCK
General Medicine
Middle Aged
medicine.disease
ADENOSINE
Endotoxemia
Pathogenesis and modulation of inflammation [N4i 1]
Clinical trial
Endocrinology
Pharmacodynamics
Female
business
Half-Life
Subjects
Details
- ISSN :
- 00316970 and 14321041
- Database :
- OpenAIRE
- Journal :
- European Journal of Clinical Pharmacology, 65(4), 393-402. Springer Verlag, European Journal of Clinical Pharmacology, 65, 4, pp. 393-402, European Journal of Clinical Pharmacology, European Journal of Clinical Pharmacology, Springer Verlag, 2008, 65 (4), pp.393-402. ⟨10.1007/s00228-008-0591-6⟩, European Journal of Clinical Pharmacology, 65, 393-402, European journal of clinical pharmacology
- Accession number :
- edsair.doi.dedup.....65f6dd7714a2a442b4b70da221456ec5