Pharmacokinetics of olanzapine after single-dose oral administration of standard tablet versus normal and sublingual administration of an orally disintegrating tablet in normal volunteers.
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.
Markowitz
John S
JS
Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston, USA.
DeVane
C Lindsay
CL
Malcolm
Robert J
RJ
Gefroh
Holly A
HA
Wang
Jun-Sheng
JS
Zhu
Hao-Jie
HJ
Donovan
Jennifer L
JL
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
D018435:ATP Binding Cassette Transporter, Subfamily B; D014150:Antipsychotic Agents; D013607:Tablets; D001569:Benzodiazepines; D004247:DNA; D000077152:Olanzapine