, Volume 40, Issue 6, pp 473-483
Date: 14 Sep 2012

Pharmacokinetics of Cyclosporin Microemulsion in Patients with Inflammatory Bowel Disease

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Abstract

Objective

To obtain a pharmacokinetic profile of cyclosporin microemulsion formulation in patients with inflammatory bowel disease.

Patients and participants

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 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 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.

Main outcome measures and 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 1607.98 μg/L and from 3612 to 7221 μg · h/L for doses of 200mg and 400mg, respectively), whereas the time to Cmax (tmax) and elimination half-life (t½β) 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, t½β 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 t½β 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.

Dr Miriam Latteri and Dr Giulia Angeloni contributed equally to this work.