Pharmacokinetics of pimecrolimus, a novel nonsteroid anti-inflammatory drug, after single and multiple oral administration.
Clin Pharmacokinet
; 42(14): 1305-14, 2003.
Article
em En
| MEDLINE
| ID: mdl-14606933
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 ANDRESULTS:
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 (C(max)) 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 C(max ) of 54.7 microg/L was measured and an AUC(24) of 589.8 microg.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.
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Base de dados:
MEDLINE
Assunto principal:
Anti-Inflamatórios não Esteroides
/
Tacrolimo
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adolescent
/
Adult
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article