title: Pharmacokinetics of olanzapine after single-dose oral administration of standard tablet versus normal and sublingual administration of an orally disintegrating tablet in normal volunteers.
abstract: Olanzapine (OLZ) is a second-generation antipsychotic agent available in 2 solid oral dosage forms, a standard oral tablet (SOT) and an orally disintegrating tablet (ODT). This study assessed the absorption of each by different routes of administration. Secondarily, the influence of P-glycoprotein (P-gp) genotype was assessed. It was hypothesized that more rapid absorption of the OLZ ODT would occur when administered sublingually versus standard oral administration. A randomized, 3-way crossover study assessed the 5-mg OLZ formulations in healthy volunteers (n = 10). Blood was collected (0-8 hours) to assess OLZ pharmacokinetics using liquid chromatography/mass spectrometry. Both routes of ODT administration resulted in more measurable early concentrations relative to SOT. However, there were no statistically significant differences observed between any of the OLZ exposures for observed pharmacokinetic parameters (C(max), T(max), AUC(0-8h)). The homozygous TT genotype for P-gp resulted in an increased AUC of OLZ for SOT administration but not for either condition where sublingual absorption could occur.
authors.affiliation: Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Markowitz
authors.forename: C Lindsay
authors.initials: CL
authors.lastname: DeVane
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Malcolm
authors.forename: Holly A
authors.initials: HA
authors.lastname: Gefroh
authors.forename: Jun-Sheng
authors.initials: JS
authors.lastname: Wang
authors.forename: Hao-Jie
authors.initials: HJ
authors.lastname: Zhu
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Donovan
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000284:Administration, Oral; D000286:Administration, Sublingual; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D000077152:Olanzapine; D013607:Tablets; D014018:Tissue Distribution
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D014150:Antipsychotic Agents; D013607:Tablets; D001569:Benzodiazepines; D004247:DNA; D000077152:Olanzapine