ABSTRACT
Lipophilicity is an important physicochemical parameter of biological relevance; although its in- vivo predictive capability is dependent on accuracy and reliability of platforms used for its determination. This work examines biomimetic attribute of isocratic chromatographic hydrophobicity index (ICHI), experimental logarithm of octanol water partition coefficient (LogP) and some computed lipophilicity indices for eight (8) selected antipsychotic agents and their predictive capability in drug discovery. The retention behavior of 5 first-generation and 3 second-generation antipsychotics was determined on reversed-phase chromatographic platform using methanol-phosphate buffer (pH 6.8) mobile phase. The retardation factor obtained was transformed to Rm, and plotted against volume fraction of organic modifier in the mobile phase to generate linear graph whose x- intercept is ICHI. Experimental LogP values were curled from literature while computed LogP were obtained using respective software. The experimentally determined LogPoctanol/water and ICHI were first correlated with index of brain permeability (BBB); before all lipophilicity indices were comparatively evaluated and correlated with in-vivo-normalized pharmacokinetic parameters curled from literature. ICHI gave better correlation with BBB index (r = 0.976) compared to Log Poctanol/water (r = 0.557). Comparative lipophilicity evaluation shows clustered pattern for second generation antipsychotics compared to first generation. In vivo correlation was poorer for the 8 drugs (r < 0.7), better with subset of phenothiazine homologues (r = 0.51 to 0.97). The ALogP, LogPoctanol/water, cLogP and ICHI gave highest correlation with the pharmacokinetic parameters. The biomimetic attributes of ICHI is better than for LogPoctanol/water in predicting brain permeability, but lower for in-vivo pharmacokinetic prediction.
Subject(s)
Humans , Biomimetics , Hydrophobic and Hydrophilic Interactions , Permeability , Antipsychotic Agents , PharmacokineticsABSTRACT
Background: Despite the fact that adherence to antipsychotic medications is the cornerstone in the treatment and prevention of relapse of the disease, non-adherence is a major problem among schizophrenia patients. The purpose of this study was to assess the magnitude and factors associated with antipsychotic medication non-adherence among schizophrenia patients in Amanuel Mental Specialized Hospital. Method: An institution-based cross-sectional study was conducted among 412 people with schizophrenia at Amanuel Mental Specialized Hospital from April to May 2014. Non-adherence was assessed using the questionnaire of Morisky medication adherence rating scale and semi-structured questions for assessment of associated factors. Logistic regression analysis was used to assess predictors of non-adherence. Results: Prevalence of non-adherence was 41.0% among schizophrenia patients. Living in rural areas (adjusted odds ratio [AOR] = 2.07; 95% confidence interval [CI]: 1.31, 3.28), current substance use (AOR = 1.67; 95% CI: 1.09, 2.56), long duration of treatment (AOR = 2.07; 95% CI: 1.22, 3.50) and polypharmacy (AOR = 2.13; 95% CI: 1.34, 3.40) were found to be significantly associated with non-adherence. Conclusion: The results indicate that non-adherence to antipsychotic medication was a major problem among patients with schizophrenia. Reducing the number of antipsychotic medications and availing drugs in rural areas may decrease the level of non-adherence
Subject(s)
Antipsychotic Agents , Ethiopia , Patients , SchizophreniaABSTRACT
Delirium is commonly encountered in the setting of paediatric consultation-liaison psychiatry. However; it is commonly misdiagnosed as current operational diagnostic criteria may be difficult to apply in children. We present a practical approach to eliciting the signs and symptoms of delirium in children and a proposed treatment algorithm which elaborates a variety of environmental management strategies and includes explicit thresholds for the use of antipsychotic medications