BackgroundAlthough it is a preventable and treatable disease, tuberculosis remains a major medical and public health problem throughout the world. The control and elimination of tuberculosis is currently challenged by the development and spread of antituberculosis drug resistance. The resistance is often correlated to the absence of properly implemented control measures that lead to poor treatment outcomes. Therefore, the aim of the current study was to assess poor treatment outcomes and its determinants among tuberculosis patients in selected health facilities in East Wollega zone, Western Ethiopia.MethodA five-year retrospective cross-sectional study design was employed. Data were collected from patients’ medical record from January to March 2017. Data were entered and analyzed using SPSS version 20. Descriptive statistics were used to generate and summarize frequencies. Univariate and multivariate logistic regression analysis were used to associate the potential determinants of poor treatment outcomes.ResultsFrom 995 patients with documented treatment outcomes, 58.9% were males with a mean age of 31.9±16.3 years and 58% lived in rural areas. Majorities of cases (95.7%) were newly treated ones. Nearly half of the cases had extrapulmonary tuberculosis and 6.8% were co-infected with HIV. Nearly three-quarter of patients had completed their treatment while 17.2%, 2.9%, 4.8%, 0.4% patients were cured, defaulted, died, and failed, respectively. The overall treatment success rate was 91.9%. Being treated in Anger Gute health center (adjusted odds ratio (AOR): 2.27; 95% confidence interval (CI): 1.18–4.38); male (AOR: 1.81; 95% CI: 1.06–3.10); lived in rural areas (AOR: 1.73; 95% CI: 1.02–2.91); previously treated (AOR: 2.72; 95% CI: 1.16–6.39) and unknown HIV status (AOR: 4.56; 95% CI: 1.98–10.50) were determinants of poor treatment outcomes.ConclusionThe current treatment success rate was exceeded the recommended target. However, special attention and strict follow up is required for tuberculosis patients with high risk of unsuccessful treatment outcomes including male, rural resident, previously treated and unknown in HIV status patients throughout their treatment periods.

Biotransformation is a process by which organic compounds are transformed from one form to another, aided by organisms such as bacteria, fungi and enzymes. It plays a major role and determines the fate of the prospective drugs. Biotransformation must take place only after the drugs reach their specific target site and produce the desired effects. In addition, the nature of the metabolites produced from the drug, must be thoroughly studied; otherwise, the drugs would be rejected during the screening process. Hence, drug metabolism is a major criterion in the highthroughput screening of prospective drugs.Biotransformation has an important role in the determination of the pharmacokinetic parameters like oral bioavailability, drug-drug interaction, clearance and the half-life of the entity within the cell. It is very essential in the toxicity studies too. Biotransformation is used as a valuable strategy to build molecules, similar to parent drug in the drug discovery programme. It can play an important role in identifying factors underlying the problems, facilitate the optimal selection of compounds for further development, provide information on metabolites for possible improvement in drug design, and contribute to the identification of the appropriate animal species for subsequent toxicity testing. Hence, some of the metabolites of biotransformation were already developed as a drug and are currently in clinical use.pharmacologically inactive compounds to pharmacologically active metabolites. These reactions are usually mediated by a broad class of hydrolytic enzymes, such as esterases, amidases and phosphotases, although the conversion of a prodrug to the corresponding active drug can also occur non-enzymatically [3][4][5][6]. Methods for generation of metabolitesIn vitro methods Subcellular fractions: Subcellular fractions prepared from organs expressing drug metabolizing enzymes include the cytosolic fraction, the S9 fraction and microsomes. Organs such as intestine, liver, kidney, lung, and skin are known to mediate xenobiotic metabolism. Liver is the major site of drug metabolism. As a result, liver subcellular fractions are often employed for studying metabolic reactions and generation of metabolites. Subcellular fractions can be used to prepare metabolites formed by a number of enzymes such as CYP, FMO, myeloperoxidase, ketoreductase, alcohol dehydrogenase, sulfotransferase, etc. [7]. Primary cell-based systems:Intact cells such as primary hepatocytes, contain both soluble and membrane-bound enzymes including the relevant cofactors at or near the appropriate physiological concentrations. As a result, they have greater physiological relevance and can mediate both phase I and phase II metabolism. Cryopreserved J o u rn al of D r u g M etaboli s m & T ox icol o g y

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The major intention to formulate and develop colon targeted tablets is to improve the therapeutic efficacy by increasing therapeutic drug concentrations in colon. The present study was aimed to develop guar gum compression coated tablets ketorolac tromethamine to achieve the colon-specific drug release. In this study, both core and compression coated tablets were prepared by direct compression method. The prepared colon targeted tablets were characterized for different pre compression evaluations. In vitro drug release studies were performed by using USP XXIV Type II dissolution apparatus in simulated gastrointestinal fluids. From the dissolution studies, the formulation F4 showed 4.72±0.76% drug release in 5 h and it was progressively increased to 99.12±0.42% in 24 h that indicates retardation of drug release in stomach and small intestine and significant amount of drug release was observed in colonic environment. The accelerated stability studies proved the stability of guar gum compression coated tablets. From the above results, achievement of colon specific drug release might be due to substanti guar gum in the upper gastrointestinal tract, but microbial degradation in the colon. In conclusion, development of microbial degradation compression coated tablets was suitable to target the ketorolac tromethamine to colon. Further the efficacy of the developed formulations has to be assessed by pharmacokinetic studies. Abstract Article InformationThe major intention to formulate and develop colon targeted tablets is to improve the therapeutic efficacy by increasing therapeutic drug concentrations in colon. The present study was aimed to develop guar gum compression coated tablets ketorolac specific drug release. In this study, both core and compression coated tablets were prepared by direct compression method. The prepared colon targeted tablets were characterized for different pre-compression and postdrug release studies were performed by using USP XXIV Type II dissolution apparatus in simulated gastrointestinal fluids. From the in vitro dissolution studies, the formulation F4 showed 4.72±0.76% drug release in 5 h and it ssively increased to 99.12±0.42% in 24 h that indicates retardation of drug release in stomach and small intestine and significant amount of drug release was observed in colonic environment. The accelerated stability studies proved the stability of m compression coated tablets. From the above results, achievement of colon specific drug release might be due to substantial integrity of the compression coated guar gum in the upper gastrointestinal tract, but microbial degradation in the colon. In sion, development of microbial degradation compression coated tablets was suitable to target the ketorolac tromethamine to colon. Further the efficacy of the developed formulations has to be assessed by pharmacokinetic studies.