title: Pharmacokinetics of pimecrolimus, a novel nonsteroid anti-inflammatory drug, after single and multiple oral administration.
abstract: OBJECTIVE
  To investigate the pharmacokinetics and tolerability of the new nonsteroid anti-inflammatory pimecrolimus (SDZ ASM 981, Elidel) after oral administration.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  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).
  
  
  CONCLUSIONS
  The results support further evaluation of the therapeutic potential of oral pimecrolimus for the treatment of inflammatory diseases.
authors: Novartis Horsham Research Centre, Horsham, West Sussex, UK.
authors: Graham
authors: G
authors: Scott
authors: Stuart A
authors: SA
authors: Osborne
authors: Gerard
authors: G
authors: Greig
authors: Stefan
authors: S
authors: Hartmann
authors: Marie-Eve
authors: ME
authors: Ebelin
authors: Pascale
authors: P
authors: Burtin
authors: Klemens
authors: K
authors: Rappersberger
authors: Michael
authors: M
authors: Komar
authors: Klaus
authors: K
authors: Wolff
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D018565:Food-Drug Interactions / Q000502:physiology; D006207:Half-Life; D006801:Humans; D008297:Male; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C117268:pimecrolimus; D016559:Tacrolimus