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 (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.
RCT Entities:
OBJECTIVE: To investigate the pharmacokinetics and tolerability of the new nonsteroid anti-inflammatory pimecrolimus (SDZASM 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 psoriasispatients). 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.
Authors: Lawrence F Eichenfield; Anne W Lucky; Mark Boguniewicz; Richard G B Langley; Robert Cherill; Katharine Marshall; Christopher Bush; Michael Graeber Journal: J Am Acad Dermatol Date: 2002-04 Impact factor: 11.527
Authors: M Grassberger; T Baumruker; A Enz; P Hiestand; T Hultsch; F Kalthoff; W Schuler; M Schulz; F J Werner; A Winiski; B Wolff; G Zenke Journal: Br J Dermatol Date: 1999-08 Impact factor: 9.302
Authors: Alexander Kapp; Kim Papp; Ann Bingham; Regina Fölster-Holst; Jean-Paul Ortonne; Paul C Potter; Wayne Gulliver; Carle Paul; Stephen Molloy; Nathalie Barbier; Mark Thurston; Yves de Prost Journal: J Allergy Clin Immunol Date: 2002-08 Impact factor: 10.793
Authors: Ulrich Wahn; Jan D Bos; Mark Goodfield; Ruggero Caputo; Kim Papp; Ahmed Manjra; Attila Dobozy; Carle Paul; Stephen Molloy; Thomas Hultsch; Michael Graeber; Robert Cherill; Yves de Prost Journal: Pediatrics Date: 2002-07 Impact factor: 7.124