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 (Cmax) relative to the tablet administration (643 vs 523 nM/L, respectively). The 90% CIs on the ratio of mean Cmax for the tablet and suspension were 0.738 and 0.914, respectively. Mean time to peak plasma concentrations (tmax) after suspension administration was 3.1 hours, whereas the tablet resulted in a mean tmax 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.