Evaluation of vanillin as a probe drug for aldehyde oxidase and phenotyping for its activity in a Western Indian Cohort.

BACKGROUND: Aldehyde oxidase (AO), a molybdoflavoenzyme, is emerging as a key player in drug discovery and metabolism. Despite having several known substrates, there are no validated probes reported for studying the activity of AO in vivo. Vanillin (4-hydroxy 3-methoxy benzaldehyde) is an excellent substrate of AO, in vitro. In the present study, vanillin has been validated as an in vivo probe for AO. Subsequently, a phenotyping study was carried out using vanillin in a subset of Indian population with 100 human volunteers. METHODS: For the purposes of in vitro probe validation, initially the metabolism of vanillin was characterized in partially purified guinea pig AO fraction. Further, vanillin was incubated with partially purified xanthine oxidase fraction and AO fractions, and liver microsomes obtained from different species (in presence and absence of specific inhibitors). For the phenotyping study, an oral dose of 500 mg of vanillin was administered to the participants in the study and cumulative urine samples were obtained up to 8 h after giving the dose. The samples were analyzed by high-performance liquid chromatography and metabolic ratios were calculated as peak area ratio of vanillic acid/vanillin. RESULTS: (a) The results of the in vitro validation studies clearly indicated that vanillin is preferentially metabolized by AO. (b) Normal distribution tests and probit analysis revealed that AO activity was not normally distributed and that 73.72% of the participants were fast metabolizers, 24.28% intermediate metabolizers, and 2% were slow metabolizers. CONCLUSIONS: Data of the phenotyping study suggest the existence of AO polymorphism, in a Western Indian cohort.

Efficacy and Tolerability of Olmesartan, Telmisartan, and Losartan in Patients of Stage I Hypertension: A Randomized, Open-label Study.

OBJECTIVES: To compare the efficacy and tolerability of losartan, telmisartan, and olmesartan as antihypertensive agents and evaluate and compare their effects on lipid profile and blood glucose. MATERIALS AND METHODS: This was a randomized, open-label, parallel-group, comparative study conducted in sixty patients of Stage I hypertension. The eligible patients were randomly allocated into three treatment groups: (1) Tablet olmesartan (20 mg), (2) Tablet telmisartan (40 mg), and (3) Tablet losartan (50 mg). Blood pressure (BP) was assessed at an interval of 2 weeks for 3 months. Fasting blood glucose (FBG) and lipid profile were estimated at baseline and then at 12 weeks. RESULTS: Olmesartan and telmisartan were more efficacious than losartan in reducing diastolic BP (DBP). There was a statistically significant decrease in mean blood glucose level (P < 0.02) after 12 weeks of treatment in telmisartan group when compared to baseline. Serum total cholesterol, triglycerides, and low-density lipoproteins decreased significantly after 12-week treatment with olmesartan and telmisartan. CONCLUSIONS: The most efficacious drug in reducing BP is Olmesartan whereas telmisartan and losartan show equal efficacy. Telmisartan shows the most favorable effects on FBG and lipid profile.

Evaluation of adherence to therapy in patients of chronic kidney disease.

OBJECTIVE: To evaluate adherence to medication and study factors associated with non-adherence in chronic kidney disease (CKD) patients. METHODS: A prospective, cross-sectional, questionnaire based study was conducted in Nephrology department of a super specialty hospital. Patients above 18 years of age, suffering from CKD from six months or more were interviewed using self-designed, semi-structured questionnaire to get information about adherence to medication, diet restriction and lifestyle modification (n = 150). Morisky medication adherence questionnaire was used to calculate overall adherence. In this higher score indicates poor adherence. Main outcome measures included prevalence of non-adherence and factors associated with the same. RESULTS: Average number of medicines taken by each patient was 8.0+1.612 (mean+SD) per day. Non-adherence to medication schedule was reported in 34% patients. Common causes of non-adherence were high cost (21.3%), complex dosing schedule (20%), fear of adverse effects (16%). Sixty-eight% patients were not aware about importance of taking each medicine. Sixteen% stopped taking medicines due to high cost. Forty-two% suggested that government should adopt measures to provide free medicines to poor patients. In Morisky medication adherence questionnaire high, medium and low adherence was reported in 7.3%, 55.3% and 37.3% of patients, respectively. Moderately positive correlation was observed between poor adherence and number of concurrent illnesses and number of medicines taken. CONCLUSION: Since majority of patients were not aware about importance of taking each medicine, creating awareness about the same is essential for improving adherence to therapy. Measures to provide free medicines to non-affording patients need to be implemented since high cost was other major cause of non-adherence.