Oral Bioavailability of Candesartan Cilexetil Suspension

Abstract

Background:

Candesartan cilexetil is a prodrug that is converted to candesartan during absorption from the gastrointestinal tract. Candesartan is a potent, orally active, specific angiotensin II type 1 receptor antagonist that has become a well-accepted treatment for hypertension. Pediatric patients often require alternative dosage forms, as candesartan cilexetil is not yet commercially available as a liquid formulation.

Objective:

To determine the relative bioavailability of candesartan by comparing a candesartan cilexetil tablet (reference formulation) with an oral candesartan cilexetil suspension (test formulation).

Methods:

In an open-label, randomized, 2 period, 2 treatment crossover study, 24 healthy volunteers were given a 32 mg candesartan cilexetil tablet and a 32 mg candesartan cilexetil suspension with a 7 day washout period between treatments.

Results:

Pharmacokinetic analyses showed that the mean relative bioavailability of the candesartan cilexetil commercial 32 mg tablet compared with the suspension of 32 mg candesartan cilexetil was 93%. The 90% CIs of the plasma AUC for the tablet versus suspension (0.861 and 0.998, respectively) were well within the bioequivalence criteria of 80–125%. Administration of candesartan cilexetil suspension was associated with a 17% increase in the maximum plasma concentration (C_max) relative to the tablet administration (643 vs 523 nM/L, respectively). The 90% CIs on the ratio of mean C_max for the tablet and suspension were 0.738 and 0.914, respectively. Mean time to peak plasma concentrations (t_max) after suspension administration was 3.1 hours, whereas the tablet resulted in a mean t_max of 3.9 hours. No significant differences in elimination half-life were observed between the 2 formulations. Both formulations were well tolerated, and no serious adverse events were reported.

Conclusions:

These results demonstrate that administration of candesartan cilexetil suspension achieves an extent of absorption and tolerability that is comparable with those of orally administered candesartan cilexetil tablets.