Effect of absorption site on the pharmacokinetics of sublingual asenapine in healthy male subjects.

Asenapine is a psychopharmacologic agent approved in the United States for the acute treatment of schizophrenia in adults and the acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features in adults. It is pending approval for the treatment of schizophrenia and manic episodes associated with bipolar I disorder in Europe. Asenapine is administered as a sublingual formulation. To determine whether the pharmacokinetics of asenapine are impacted by placing the tablet buccally ('cheeking') or allowing the tablet to dissolve on the top of the tongue, pharmacokinetics were compared following buccal and supralingual administration versus sublingual administration. In this open-label, randomized, 3-way crossover trial, healthy men (n=36) received single 5 mg doses of asenapine via sublingual, supralingual and buccal routes, at least 1 week apart. With buccal administration, the area under the concentration-over-time curve (AUC(0-infinity)) and peak concentration (C(max)) were, respectively, 24%, and 19% higher than with sublingual administration; these routes were not bioequivalent. With supralingual administration, AUC(0-infinity) and C(max) were 6% and 13% lower than with sublingual administration; bioequivalence was established based on AUC(0-infinity) only; bioequivalence based on C(max) could not be assessed due to 40% within-subject variability. The most common adverse events were oral paresthesia (sublingual, 75.8%; supralingual, 55.9%; buccal, 45.7%) and somnolence (81.8%; 76.5%; 68.6%). Compared with the recommended sublingual route of asenapine administration, exposure was 24% higher with buccal administration and comparable to supralingual administration. However, differences in exposure associated with variable placement in the oral cavity did not compromise safety in healthy subjects.