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
Direct effects of Nauclea latifolia extracts on different gastrointestinal nematodes of sheep is described. In vivo and in vitro studies were conducted to determine possible anthelmintic effect of leaf extracts of Nauclea latifolia toward different ovine gastro intestinal nematodes. A larval development assay was used to investigate in vitro; the effect of aqueous and ethanolic extracts of N. latifolia towards strongyles larvae. The development and survival of infective larvae (L3) was assessed and best-fit LC50 values were computed by global model of non-linear regression analysis curve-fitting (95CI). Twenty sheep harbouring naturally acquired gastrointestinal nematodes were treated with oral administration of ethanolic extracts at a dose rate of 125 mg/kg; 250 mg/kg and 500mg/kg to evaluate therapeutic efficacy; in vivo. The presence of the extracts in the cultures decreased the survival of larvae. The LC50 of aqueous and ethanolic extract were 0.704 and 0.650 mg/ml respectively and differ significantly (P0.05; paired t test). Faecal egg counts (FEC) on day 12 after treatment showed that the extract is effective; relative to control (1-way ANOVA; Dunnett's multiple comparison test); at 500mg/kg against Haemonchus spp; Trichostrongylus spp (p0.05); Strongyloides spp (P 0.01); at 250mg/kg against Trichuris spp (P 0.01) and ineffective against Oesophagostomum spp (p0.05). The effect of doses is extremely significant; the day after treatment is sometimes significant while interaction between dose and day after treatment is insignificant (2-way ANOVA). N. latifolia extract could therefore find application in the control of helminth in livestock; by the ethnoveterinary medicine approach