title: Pharmacokinetics of cyclosporin microemulsion in patients with inflammatory bowel disease.
abstract: OBJECTIVE
  To obtain a pharmacokinetic profile of cyclosporin microemulsion formulation in patients with inflammatory bowel disease.
  
  
  METHODS
  58 consecutive patients (19 women and 39 men), aged 16 to 64 years (mean age 38 years), with a diagnosis of ulcerative colitis (29 patients) or Crohn's disease (29 patients).
  
  
  METHODS
  Patients were treated with oral doses of cyclosporin microemulsion ranging from 200 to 400 mg daily. Blood samples were collected after 7 days of treatment; blood was drawn at 0, 0.5, 1, 2, 3, 5, 7 and 12 hours after the morning dose. In 23 patients out of 29 with ulcerative colitis and 23 out of 29 with Crohn's disease, these profiles were repeated immediately before hospital discharge, which took place an average of 18 days after admission. Blood specimens were assayed for cyclosporin immunoreactivity on the day of blood withdrawal by a radioimmunoassay technique.
  
  
  RESULTS
  In the range of doses employed, the average peak plasma drug concentration (Cmax) and area under the concentration-time curve to 12 hours tended to increase linearly with the dose (from 782.35 to 1,607.98 microg/L and from 3,612 to 7,221 microg x h/L for doses of 200 mg and 400 mg, respectively), whereas the time to Cmax (tmax) and elimination half-life (t 1/2beta) ranged between 78 and 95.2 min and 85.5 and 162 min, respectively, and did not appear to change with the dose. After dose-normalisation by transformation of data into percentage increase over baseline (trough) concentration for each patient, single kinetic parameters for the whole study population (n = 58) could be calculated (Cmax 620% vs baseline. tmax 86.5 min, t 1/2 115 min). Comparison between patients with Crohn's disease and ulcerative colitis showed that the latter had higher Cmax values (702% compared with 543% vs baseline, p < 0.05) whereas tmax and t 1/2beta values overlapped.
  
  
  CONCLUSIONS
  The pharmacokinetic parameters of cyclosporin microemulsion in patients with inflammatory bowel disease are broadly similar to those previously measured in healthy volunteers and in other disorders requiring cyclosporin treatment.
authors.affiliation: Institute of Internal Medicine, Catholic University Medical School, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Latteri
authors.forename: G
authors.initials: G
authors.lastname: Angeloni
authors.forename: N G
authors.initials: NG
authors.lastname: Silveri
authors.forename: R
authors.initials: R
authors.lastname: Manna
authors.forename: G
authors.initials: G
authors.lastname: Gasbarrini
authors.forename: P
authors.initials: P
authors.lastname: Navarra
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004655:Emulsions; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine