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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 14/2003

01-12-2003 | Original Research Article

Pharmacokinetics of Pimecrolimus, a Novel Nonsteroid Anti-Inflammatory Drug, After Single and Multiple Oral Administration

Authors: Graham Scott, Stuart A. Osborne, Gerard Greig, Stefan Hartmann, Dr Marie-Eve Ebelin, Pascale Burtin, Klemens Rappersberger, Michael Komar, Klaus Wolff

Published in: Clinical Pharmacokinetics | Issue 14/2003

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Abstract

Objective: To investigate the pharmacokinetics and tolerability of the new nonsteroid anti-inflammatory pimecrolimus (SDZ ASM 981, Elidel®) after oral administration.
Design: A single-dose, randomised, double-blind, placebo-controlled, dose-rising, parallel-group study in healthy male volunteers, and a multiple-dose, randomised, double-blind, placebo-controlled, dose-rising study in patients with psoriasis.
Setting: One centre in France (single-dose study) and one centre in Austria (multiple-dose study).
Methods: The first study investigated the pharmacokinetics and tolerability of ascending single oral doses of pimecrolimus (5–60mg). The 60mg dose was repeated in the same subjects after a fat-rich breakfast. The second study investigated the pharmacokinetics, tolerability, safety and efficacy of rising oral doses administered once daily (5–20mg) or twice daily (20 and 30mg) for 28 days. Only the pharmacokinetic, safety and tolerability data of this study are presented.
Outcome measures and results: Oral administration of pimecrolimus was well tolerated up to the highest dose (60mg). Pimecrolimus was rapidly absorbed (time to maximum blood concentration 0.7–2 hours). A high-fat meal before drug administration delayed the time to peak concentration. Blood concentrations appear to have a long-terminal half-life (30–40 hours after a single dose in fasted subjects, 50–100 hours after the final dose on day 28 in psoriasis patients). After multiple doses, steady state was attained after 6–13 days. Maximum blood concentrations (Cmax) and exposure (area under the concentration-time curve; AUC) were broadly dose proportional. At the highest dose administered in the multiple-dose study (30mg twice daily), a Cmax of 54.7 µg/L was measured and an AUC24 of 589.8 µg · h/L was calculated at steady state (day 13).
Conclusion: The results support further evaluation of the therapeutic potential of oral pimecrolimus for the treatment of inflammatory diseases.
Footnotes
1
Use of tradenames is for product identification only and does not imply endorsement.
 
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Metadata
Title
Pharmacokinetics of Pimecrolimus, a Novel Nonsteroid Anti-Inflammatory Drug, After Single and Multiple Oral Administration
Authors
Graham Scott
Stuart A. Osborne
Gerard Greig
Stefan Hartmann
Dr Marie-Eve Ebelin
Pascale Burtin
Klemens Rappersberger
Michael Komar
Klaus Wolff
Publication date
01-12-2003
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 14/2003
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.2165/00003088-200342140-00006

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