Understanding the Oral Mucosal Absorption and Resulting Clinical Pharmacokinetics of Asenapine

Abstract

Absorption of drugs from the oral cavity into the mucosal tissues is typically a fast event. Dissolved drugs partition into the mucosal membranes and within minutes will reach equilibrium with drug in solution in the oral cavity. However, this does not always equate to rapid drug appearance in the systemic circulation. This has been attributed to slow partitioning out of the mucosal tissues and into the systemic circulation. Based on information from literature, physicochemical properties of asenapine, and clinical data, we conclude that for sublingually administered asenapine, the exposure is primarily a function of rapid partitioning into the mucosal membranes. This is followed by slow partitioning out of the mucosal tissues and into the systemic circulation, leading to a T (max) value of about 1 h. The bioavailability of asenapine at doses below the saturation solubility in the mouth does not change and is controlled primarily by mass transport equilibrium. At doses above the saturation solubility, the bioavailability becomes more dependent not only on the distribution equilibrium but also on contact time in the mouth because additional variables (e.g. dissolution rate of the drug) need to be accounted for. These explanations are consistent with oral cavity absorption models from the literature and can be used to accurately describe the clinical data for asenapine.

Pharmacokinetics of a Novel Sublingual Spray Formulation of the Antimalarial Drug Artemether in Healthy Adults

“…In addition, the first peak does not involve FP metabolism. Drug absorption during the first phase accounted for between 32% and 69% (RATIO, 0.48 and 2.23, respectively) of the total dose and was consistent with that seen in the case of other sublingually absorbed drugs (27). The lower relative bioavailability of the 15.0-mg dose versus the 30.0-mg ArTiMist doses, together with a comparison of the present AUC 0 -ϱ /dose data and those of previously published studies, suggest that artemether has dose-dependent pharmacokinetics.…”

Novel and revisited approaches in nanoparticle systems for buccal drug delivery

“…The accessible surface area for drug absorption in the oral cavity is small, about 50 cm 2 The saliva is the most relevant hampering factor, since its renovation cycles may dilute the drug concentration at the absorption site leading to a low drug amount at the surface of the buccal mucosa [31]. Also, the swallowing of the saliva or the ingestion of food may cause the removal of the drug from the absorption site ( Figure 3).…”

New approaches for the management of bipolar disorder: role of sublingual asenapine in the treatment of mania

“…Bioavailability is 35% with sublingual administration but <2% if asenapine is ingested; because absorption is also decreased in the presence of food or liquid, oral intake must be avoided for 10 minutes after taking the medication. At doses above the saturation solubility, bioavailability becomes dependent on the distribution equilibrium and also on contact time in the mouth 57. Compared with the sublingual route, asenapine exposure is 24% higher with buccal and supralingual administration administration 58.…”