Pharmacokinetics of cyclosporin microemulsion in patients with inflammatory bowel disease

Objective: To obtain a pharmacokinetic profile of cyclosporin microemulsion formulation in patients with inflammatory bowel disease. Patients and part icipants: 58 consecutive patients (19 women and 39 men), aged 16 to 64 year s (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 400mg 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 o ut of 29 with Crohn's disease, these profiles were repeated immediately bef ore hospital discharge, which took place an average of 18 days after admiss ion. Blood specimens were assayed for cyclosporin immunoreactivity on the d ay of blood withdrawal by a radioimmunoassay technique. Main outcome measures and results: In the range of doses employed, the aver age peak plasma drug concentration (C-max) and area under the concentration -time curve to 12 hours tended to increase linearly with the dose (from 782 .35 to 1607.98 mug/L and from 3612 to 7221 mug (.) h/L for doses of 200mg a nd 400mg, respectively), whereas the time to C-max (t(max)) and elimination half-life (t1/2 beta) 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-norma lisation by transformation of data into percentage increase over baseline ( trough) concentration for each patient, single kinetic parameters for the w hole study population (n = 58) could be calculated (C-max 620% vs baseline, t(max) 86.5 min, t1/2 beta 115 min). Comparison between patients with Croh n's disease and ulcerative colitis showed that the latter had higher Cmax v alues (702% compared with 543% vs baseline, p < 0.05) whereas tmax and t1/2 beta values overlapped. Conclusions: The pharmacokinetic parameters of cyclosporin microemulsion in patients with inflammatory bowel disease are broadly similar to those prev iously measured in healthy volunteers and in other disorders requiring cycl osporin treatment.