%0 Journal Article
%T Relative bioavailability of single doses of prolonged-release tacrolimus administered as a suspension, orally or via a nasogastric tube, compared with intact capsules: a phase 1 study in healthy participants
%A James Dickinson
%A Nasrullah Undre
%J -
%D 2017
%R 10.1136/bmjopen-2016-012252
%X Objective Tacrolimus, an immunosuppressant widely used in solid organ transplantation, is available as a prolonged-release capsule for once-daily oral administration. In the immediate postsurgical period, if patients cannot take intact capsules orally, tacrolimus therapy is often initiated as a suspension of the capsule contents, delivered orally or via a nasogastric tube. This study evaluated the relative bioavailability of prolonged-release tacrolimus suspension versus intact capsules in healthy participants.

Design A phase 1, open-label, single-dose, cross-over study.

Setting A single clinical research unit.

Participants In total, 20 male participants, 18每55ˋyears old, entered and completed the study.

Interventions All participants received nasogastric administration of tacrolimus 10ˋmg suspension in treatment period 1, with randomisation to oral administration of suspension or intact capsules in periods 2 and 3. Blood concentration每time profile over 144ˋhours was used to estimate pharmacokinetic parameters.

Primary and secondary outcome measures Primary end point: relative bioavailability of prolonged-release intact capsule versus oral or nasogastric administration of prolonged-release tacrolimus suspension (area under the concentration每time curve (AUC) from time 0 to infinity post-tacrolimus dose (AUC0每﹢); AUC measured until the last quantifiable concentration (AUC0每tz); maximum observed concentration (Cmax); time to Cmax (Tmax)). Tolerability was assessed throughout the study.

Results Relative bioavailability of prolonged-release tacrolimus suspension administered orally was similar to intact capsules, with a ratio of least-square means for AUC0每tz and AUC0每﹢ of 1.05 (90% CI 0.96 to 1.14). Bioavailability was lower with suspension administered via a nasogastric tube versus intact capsules (17%; ratio 0.83; CI 0.76 to 0.92). Cmax was higher for oral and nasogastric suspension (30% and 28%, respectively), and median Tmax was shorter (difference 1.0 and 1.5ˋhours postdose, respectively) versus intact capsules (2.0ˋhours). Single 10ˋmg doses of tacrolimus were well tolerated.

Conclusions Compared with intact capsules, the rate of absorption of prolonged-release tacrolimus from suspension was faster, leading to higher peak blood concentrations and shorter time to peak; relative bioavailability was similar with suspension administered orally
%U https://bmjopen.bmj.com/content/7/4/e012252