Olanzapine Pharmacokinetics: A Clinical Review of Current Insights and Remaining Questions.

Olanzapine is one of the most widely used antipsychotics since its initial approval by the US Food and Drug Administration in 1996 and has undergone extensive pharmacokinetic study. Despite being utilized in clinical psychiatry for decades, there remain questions regarding the variety of available formulations, the utility of therapeutic drug monitoring, altered kinetic properties in special populations/medical illnesses, the use of high-dose olanzapine, and drug interactions, among many others. We performed a narrative literature review of olanzapine pharmacokinetics in June 2023 using the US National Library of Medicine's PubMed.gov resource (https://www.ncbi.nlm.nih.gov/pubmed) and Google Scholar. Herein, we review clinically relevant aspects of olanzapine pharmacokinetic data while highlighting knowledge gaps and potential areas of future study.

Predictors of civil and forensic inpatient psychiatric readmissions at a Public Mental Health Hospital.

Inpatient psychiatric readmissions are increasingly prevalent and associated with worse prognostic outcomes and high economic costs, regardless of the medicolegal ramifications that necessitate them. Unlike most general medical readmissions, psychiatric readmissions are commonly warranted for both medical and legal purposes. However, studies focusing on analyzing the predictors of inpatient psychiatric readmission and their relationship to civil versus forensic readmission are limited. The purpose of this study was to examine the predictors of psychiatric readmission among civil and forensic patients admitted to a psychiatric hospital. In this retrospective chart review, we extrapolated data from medical records of 741 patients admitted from 2012 to 2017 with follow up until 2019. Analyses involved chi-square tests for comparing the distribution of demographic and clinical variables between forensic and civil readmission, and Cox regression to determine predictors of time to first readmission. Our results show that race, diagnosis, restraint/seclusion, type of admission, and disposition are significantly associated with an increased risk of psychiatric readmission. This study has important implications for healthcare providers and policy makers in revising mental health policies and improving systems-based practices for the mental health system. Future efforts in improving community psychiatric services and enhancing inpatient therapeutic environment may reduce psychiatric readmissions.

A PCR-based quantitative assay for the evaluation of mRNA integrity in rat samples.

Reverse Transcription quantitative real-time PCR (RT-qPCR) is applied to quantify gene transcript levels in a wide range of investigations. Proper assessment of RNA integrity is essential for reliable assessment of gene expression levels, as RNA molecules are acutely vulnerable to degradation. However, RNA quality control measures are still infrequently reported in rat toxicological studies, which impede proper evaluation of gene expression data reliability. The high operational cost of microfluidic capillary electrophoresis systems along with paucity of alternative methods for the quantitative assessment of rat RNA integrity constitute potential hurdles to the systematic implementation and reporting of RNA integrity assessment in rat studies. This manuscript describes the adaptation of an alternative RT-qPCR-based 3':5' assay as an additional option for the quantitative assessment of rat RNA integrity. Two PCR primer sets were designed on the 3' and 5' regions of a rat housekeeping gene to evaluate RNA integrity by measuring the relative expression (3':5' ratio) of these amplicons. The 3':5' ratios were then compared to Agilent Bioanalyzer's RNA integrity number (RIN) for a wide range of RNA samples originating from different tissues, cultured cell lines and rat strains that were prepared freshly, stored for years at -80 °C, purchased commercially or intentionally degraded. The 3':5' ratios and RIN values presented similar assessment of RNA integrity status from intact to heavily degraded samples. Based on the LOWESS regression of this large comparison dataset, 3':5' ratio threshold criteria equivalent to RIN cut-off values can be proposed for the selection of RNA samples for RT-qPCR analyses. This qPCR-based assay is easy to implement, cost-effective, and provides a reliable quantification of RNA integrity to assist in the selection of rat RNA samples suitable for downstream RT-qPCR gene expression analyses.

Perinatal methylmercury exposure perturbs the expression of Plp1 and Cnp splice variants in cerebellum of rat pups.

Early life exposure to environmental chemicals can interfere with myelin formation in the developing brain, leading to neurological disorders. The Proteolipid Protein 1 (Plp1), Myelin Basic Protein (Mbp) and 2',3'-Cyclic Nucleotide 3'Phosphodiesterase (Cnp) genes expressed in oligodendrocytes and involved in myelination processes can be useful biomarkers of potential developmental neurotoxicity. In an earlier study, we concluded that the reduction in the expression levels of Mbp splice variants in juvenile rat cerebellum following perinatal methylmercury (MeHg) exposure were compatible with an overall reduction of mature oligodendrocytes population. This observation prompted us to analyze the expression of Plp1 and Cnp in developing rat cerebellum to further confirm and investigate the toxic effects of MeHg on vulnerable oligodendrocytes. Splice variants of Plp1 in human and of Cnp in mouse are curated in NCBI RefSeq database, but not for rat. Lack of annotation of splice variants can pose significant challenge for the reliable quantification of gene expression levels in toxicological studies. Therefore, we applied a "comparative sequence analysis" approach, relying on annotated splice variants in human/mouse and on evolutionary conservation of intron-exon structures, to identify additional splice variants of Plp1 and Cnp in rat. Then, we confirmed their identity by nucleotide sequencing and characterized their temporal expression patterns during brain development by RT-PCR. The measurement of total transcripts and individual splice variants of Plp1 and Cnp in the cerebellum of MeHg-exposed rat pups revealed a relatively similar level of reduction in their expression levels. This study further confirms that perinatal exposure to MeHg can impact oligodendrocytes in pups. Based on these observations, we conclude that monitoring the expression of these oligodendrocyte-enriched genes can be useful to identify toxic chemicals affecting myelination.