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.

Aim:To compare adherence to American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) 2015 guidelines for diabetes care in a tertiary care teaching hospital in India. Method: In this prospective observational study, 415 prescriptions of type 2 diabetes mellitus (T2DM) patients were collected in Dr. Pinnamaneni Siddhartha Institute of Medical Sciences (PSIMS) hospital from January 2015 and June 2015. Medication adherence to AACE/ACE guidelines was assessed based on glycated haemoglobin (HbA1C) values. Results: A total of 201 (48.4%) male and 214 (51.6%) female patients were identified. The mean age was 53.57 ± 10.77 years (male) and 53.69 ± 10.71 years (females). Patients with HbA1C <7.5% (37.3%, male; 45.3%, female) were predominant followed by HbA1C 7.5% -9% (32.3%, male; 35.3%, female) and HbA1C > 9.0% (30.4%, male; 19.2%, female). Hypertension (HTN) (39.8%, male; 39.7%, female) is the most predominant co-morbidity, followed by patients with both HTN and cardio vascular diseases (CVDs) (9.4%, male; 9.8%, female). Insulin was prescribed to control hyperglycaemia in most of the cases (40.0%) followed by dual therapy (26.9%) and triple therapy (17.8%). The overall adherence rate was 88.3% for patients with HbA1C <7.5% (P< 0.0001); 98.7% for patients with HbA1C 7.5%-9%(P<0.0001)and 100% for patients with HbA1C >9%(P<0.0001). Conclusion: Optimal medication adherence is the ultimate goal to control the hyperglycemia in DM. The present study results revealed that the anti-diabetic medication adherence to AACE/ACE 2015 guidelines were optimal by the prescribers.