Cytochrome P-450 (CYP) enzymes and P-glycoprotein (P-gp) play an important role in the oral bioavailability and first-pass-metabolism (FPM) of many drugs. Rasagiline is a selective, monoamine oxidase-B inhibitor and it undergoes significant FPM in the liver prior to excretion by CYP1A2. Hesperetin and naringenin are naturally occurring flavanones and are reported as modulators of CYP enzymes and P-gp. The objective of the present investigation was to evaluate the effect of hesperetin and naringenin on the pharmacokinetics (PK) of rasagiline in rats. Rats were treated orally with rasagiline (2 mg/kg) alone and co-administered with hesperetin and naringenin (12.5 and 25 mg/kg) for 15 consecutive days. Blood samples were collected from tail vein on the 1st day in a single dose PK study (SDS) and on 15th day in the multiple dose PK study (MDS). Hesperetin and naringenin co-administration significantly enhanced the area under the curve (AUC), maximum plasma concentration (Cmax) and elimination half life (t1/2) of rasagiline with a concomitant reduction in clearance (CL/F) in both SDS and MDS. Rasagiline concentrations were significantly increased when co-administered with hesperetin and naringenin in the brain. No significant difference was found in rasagiline transport from mucosal to serosal side in the presence of hesperetin and naringenin ex vivo (rat everted gut sacs used). Our findings suggested that hesperetin and naringenin enhanced the systemic exposure of rasagiline might be through the inhibition of CYP1A2 but not P-gp. Further studies are needed on CYP1A2 and P-gp over expressed cells to confirm this interaction at cellular level.
N‐acetyl‐p‐benzoquinoneimine (NAPQI) is toxic metabolite of paracetamol formed primarily by cytochrome P4502E1 (CYP2E1) metabolic pathway when administered at therapeutic doses or overdose. The influence of quercetin (flavonoid) on the bioactivation of paracetamol to NAPQI was investigated using rat liver microsomes and rats in vivo. Paracetamol (80 mg/kg) was administered orally without or with silymarin (100 mg/kg), a known inhibitor of CYP2E1, CYP3A4 and quercetin (10 and 20 mg/kg) to rats for 15 consecutive days. Area under the plasma concentration–time curve (AUC0‐∞) and the peakplasma concentration (Cmax) of paracetamol were dose‐dependently increased with quercetin (10 and 20 mg/kg) compared to paracetamol control group (p < 0.001). On the other hand, the AUC0‐∞ and Cmax of NAPQI were decreased significantly with quercetin. The same results were observed with silymarin also. The elevated liver and kidney functional enzymes/compounds were significantly reduced by quercetin and silymarin compared to paracetamol control group. The formation of NAPQI was reduced in the incubation samples in presence of quercetin in experiment using isolated rat hepatocytes. The presentstudy results revealed that quercetin might be inhibited the CYP2E1‐mediated metabolism of paracetamol; thereby decreased the formation of NAPQI and protected the liver and kidney.
Diabetic retinopathy (DR) is a leading cause of visual impairment and blindness in the working-age population across the globe. The objective of the present study was to assess the drug utilization pattern, risk factors and prevalence of diabetic retinopathy in patients with type 2 diabetes mellitus in a south Indian tertiary care hospital. A cross-sectional observational study was conducted on 745 subjects (386 with diabetic retinopathy and 359 without diabetic retinopathy). Prevalence of diabetic retinopathy was measured and risk factors for the development of diabetic retinopathy were determined by calculating odds ratios using graph-pad prism statistical software and drug utilization pattern was assessed. Retinopathy was significantly higher in the subjects who are married, uneducated, housewives, urban residents, no income group and risk factors were comorbidities (other diseases, hypertension, endocrine diseases, history of cardiovascular diseases, HbA1c, high serum creatinine, duration of diabetes (5-10 years and >10 years, physical inactivity, junk foods (weekly once and weekly twice), soft drinks occasionally and tea/ coffee (daily twice). Metformin (38.21%), combination of Insulin Isophane and Insulin Regular (16.75%), Insulin Regular (15.18%), combination of Glimepiride and Metformin (11.51%), Glimepiride (7.85%), combination of Metformin and Vildagliptin (7.85%) were most commonly prescribed anti-diabetic drugs to the T2DM patients with retinopathy. The present study revealed that risk factors for the development of diabetic retinopathy were multiple
Background: Type 2 diabetes mellitus (T2DM) is the most general type of diabetes. In India, the risk factors (modifiable and nonmodifiable) for diabetes are seen more frequently and there is lack of perception about this problem.Objective: The objective of the study was to assess the incidence and risk factors for T2DM in a south Indian tertiary care hospital.Materials and Methods: A prospective study was conducted on 1161 subjects (with or without T2DM) from November 2014 to April 2015 in general medicine department of Dr. Pinnamaneni Siddhartha Institute of Medical Sciences and Research Foundation, Andhra Pradesh, south India. Chi-square test was used to evaluate the incidence of T2DM and odds ratios were calculated in univariate logistic regression analysis for risk factors.Results: T2DM was significantly higher in the subjects of age above 41 years (86.3%, P<0.0001), married (95.4%, P=0.002), educators (degree and above, 13.2%, P<0.0001), known family history (50.8%, P<0.0001), BMI (>25 kg/m2,58.7%; P<0.0001), Govt. job holders (5.5%, P<0.0001), business people (12%, P<0.0001), house wives (38.3%, P<0.0001), high economic status (34.9%, P<0.0004), preexisting hypertension (40.2%, P<0.0001), urban residence (50.4%, P<0.0001), physical inactivity (45.3%, P<0.001), stress (61.0%, P=0.01), consumption of tea and coffee (daily thrice or more, 6.3%, P=0.0003), soft drinks (weekly thrice or more, 4%, P=0.0008) and junk foods (weekly thrice or more 2.6%, P=0.025) than non-diabetic subjects. Univariate logistic regression analysis showed that the age (above 41 years), marital status, education, family history, BMI (>25 kg/m2), high economic status, co-morbidities (hypertension and thyroid disorders) urban residence, physical inactivity, stress, consumption of tea and coffee (daily thrice or more), soft drinks (weekly thrice or more) and junk foods are the significantly risk factors for T2DM.Conclusion: The present study results suggested that beware of hypertension, thyroids disorders, physical inactivity, stress, soft drinks and junk foods, which are major risk factors of T2DM.
Objective: The objective of the study was to assess the drug utilization pattern, medication adherence to Joint National Committee (JNC-7) treatment guidelines and risk factors for hypertension (HTN) in a south Indian tertiary care teaching hospital. Methods: A prospective study was conducted on 1000 subjects (with or without hypertension) from November 2015 to April 2016 in a general medicine department. Drug utilization pattern, medication adherence was assessed by comparing with the JNC-7 guidelines and the odds ratios were calculated in univariate regression analysis for risk factors. Results: Stage 1 hypertension (47.30%) was most predominant than stage 2 hypertension (24.28%) and hypertension emergency (12.23%) according to the SBP of JNC-7 guidelines. Hypertension was significantly higher in the subjects of age above 40 years (92.6%, P<0.0001), married (99.6%, P<0.0001), educated (59.5%, P=0.066), known family history (father, P=0.009; mother, P<0.0001; father and mother, P<0.0001), physical inactivity (74.8%, P<0.001), monthly income above Rs. 10,000 (34.5%, P<0.0001), co-morbidities (diabetes, P<0.0001; history of cardiovascular diseases, P<0.0001; chronic kidney disease, P<0.0001), alcohol consumption (19.2%, P=0.007), smoking (23%, P=0.0005), tea consumption (twice or more per day, P=0.027), and intake of junk foods (thrice or more in a week, P<0.0001) than normotensive subjects. Angiotensin receptor blockers (17.98%) are most widely prescribed drugs followed by calcium channel blockers (10.07%) and ß-blockers (6.29%) in monotherapy (38.63%). Angiotensin receptor blocker + diuretic combination (24.64%) was mostly used in two drug combination therapy (36.11%). The overall rate of adherence was 24.9% (Pre hypertension, P<0.01); 80.3% (Stage 1 hypertension, P<0.001); 73.93% (Stage 2 hypertension, P<0.001) and 50% (Hypertension emergency, P<0.05). Univariate regression analysis showed that age (above 40 years), female gender, married, widowed, generalized obesity, moderate to high economic status (Above 10, 000/month), family history, diabetes, history of cardiovascular diseases, chronic kidney disease, physical inactivity, smoking, alcohol consumption and junk food (weekly thrice or more, odds ratio: 17.69, 95% confidence interval: 2.373-131.8, P<0.0001) intake were significantly associated with HTN. Conclusion: The present study results suggested that medication adherence to JNC-7 was optimal. Junk foods, age (above 60 years), diabetes, alcohol, smoking, marital status and high economic status are the main risk factors for hypertension.
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