Dexlansoprazole 60 mg (MR) · Hard-gelatin capsules

Dexlansoprazole belongs to a class of antisecretory compounds, the substituted benzimidazoles, that suppress gastric acid secretion by specific inhibition of the (H+, K+)-ATPase at the secretory surface of the gastric parietal cell. Because this enzyme is regarded as the acid (proton) pump within the parietal cell, dexlansoprazole has been characterized as a gastric proton-pump inhibitor, in that it blocks the final step of acid production.

The dual delayed-release formulation of dexlansoprazole capsules results in a dexlansoprazole plasma concentration-time profile with two distinct peaks; the first peak occurs one to two hours after administration, followed by a second peak within four to five hours (see Figure 1). Dexlansoprazole is eliminated with a half-life of approximately one to two hours in healthy subjects and in patients with symptomatic GERD. No accumulation of dexlansoprazole occurs after multiple, once daily doses of dexlansoprazole delayed-release capsules 30 or 60 mg although mean AUCt and Cmax values of dexlansoprazole were slightly higher (less than 10%) on Day 5 than on Day 1.

The pharmacokinetics of dexlansoprazole are highly variable, with percent coefficient of variation (%CV) values for Cmax, AUC, and CL/F of greater than 30% (see Table 6).

Absorption — After oral administration of dexlansoprazole delayed-release capsules 30 or 60 mg to healthy subjects and symptomatic GERD patients, mean Cmax and AUC values of dexlansoprazole increased approximately dose proportionally (see Figure 1).

When granules of dexlansoprazole delayed-release capsules 60 mg are mixed with water and dosed via NG tube or orally via syringe, the bioavailability (Cmax and AUC) of dexlansoprazole was similar to that when dexlansoprazole delayed-release capsules 60 mg was administered as an intact capsule [see Dosage and Administration (2.3)].

Effect on Food — In food-effect studies in healthy subjects receiving dexlansoprazole delayed-release capsules under various fed conditions compared to fasting, increases in Cmax ranged from 12 to 55%, increases in AUC ranged from 9 to 37%, and Tmax varied (ranging from a decrease of 0.7 hours to an increase of three hours) [see Dosage and Administration (2.3)].

Distribution — Plasma protein binding of dexlansoprazole ranged from 96 to 99% in healthy subjects and was independent of concentration from 0.01 to 20 mcg/mL. The apparent volume of distribution (Vz/F) after multiple doses in symptomatic GERD patients was 40 L.