title: Pharmacokinetics of olanzapine long-acting injection: the clinical perspective.
abstract: Olanzapine long-acting injection (OLAI) is a sustained-release depot antipsychotic for the treatment of schizophrenia in adults. Our objective was to explain the pharmacokinetics of OLAI to provide clinical insight. Simulation models and data from clinical trials are presented. Olanzapine concentrations were observed immediately upon injection. Half-life was ∼30 days, controlled by the slow rate of intramuscular absorption rather than the 30-h elimination rate-based half-life of oral olanzapine. As each injection builds on the drug still being released from previous injections, concentrations increase gradually until a steady state is reached after ∼3 months. Concentrations were similar to oral olanzapine and proportional to the dose; the average steady-state concentrations (10th-90th percentile) for the 150, 210, and 300 mg/2-week doses were 16-32, 15-55, and 20-67 ng/ml, respectively, and those for the 300 and 405 mg/4-week doses were 19-48 and 19-62 ng/ml, respectively. Peak concentrations most often occurred at 2-4 days after injection. Peak-to-trough fluctuation was greater for the 4-week dosing interval than the 2-week one, with no apparent clinical ramifications for these differences. Trough concentrations were above the lower end of the therapeutic range, even at the first injection. Long-term use up to 6 years indicated no additional accumulation. The impact of smoking and sex was similar, but less pronounced than for oral olanzapine.
authors.affiliation: aKlinik und Poliklinik für Psychiatrie und Psychotherapie der Technischen Universität München am Klinikum rechts der Isar, München bLilly Deutschland GmbH, Klinische Forschung, Neurologie und Psychiatrie, Bad Homburg, Germany cLilly Research Laboratories dIndiana University School of Medicine and Butler University College of Pharmacy and Health Sciences, Indianapolis, Indiana, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Heres
authors.forename: Susanne
authors.initials: S
authors.lastname: Kraemer
authors.forename: Richard F
authors.initials: RF
authors.lastname: Bergstrom
authors.forename: Holland C
authors.initials: HC
authors.lastname: Detke
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003198:Computer Simulation; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D000077152:Olanzapine; D012727:Sex Characteristics; D012907:Smoking / Q000097:blood; D013997:Time Factors; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D001569:Benzodiazepines; D000077152:Olanzapine