INFLUENCE OF POMEGRANATE JUICE ON THE CYP3A4-MEDIATED METABOLISM AND P-GLYCOPROTEIN MEDIATED TRANSPORT OF SAQUINAVIR IN VIVO AND EX VIVO MODELS

Cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) play an important role in the first pass metabolism thereby limits the oral bioavailability of many clinically important and frequently prescribed drugs. The absolute oral bioavailability of saquinavir is very low (i. e. 4%) due to its extensive first pass metabolism by the major metabolizing isozyme CYP3A4 and it is also a substrate of P-gp. Pomegranate juice (PGJ) was known to be a modulator of CYP3A4 and P-gp. Therefore, the aim of this study was to evaluate the influence of PGJ on the pharmacokinetics (PK) of saquinavir in wistar rats and on the P-gp mediated intestinal transport of saquinavir in everted gut sacs ex vivo.  Rats were treated orally with saquinavir (100 mg/kg) alone and in combination with PGJ (0.5, 1.0 and 2.0 mL/200g, body weight) for 15 consecutive days. Blood samples were collected on 1st day in single dose pharmacokinetic study (SDS) and on 15th day in multiple dose pharmacokinetic study (MDS). The peak plasma concentration (Cmax)and area under the plasma concentration-time curve (AUC0-24) of saquinavir was increased with PGJ in SDS (p<0.001) may be due to inhibition of CYP3A4 and P-gp. But interestingly, the Cmax and AUC0-24 of saquinavir was decreased significantly with PGJ in MDS. This is may be due to induction of CYP3A4. The transport of saquinavir was increased in presence of PGJ and known P-gp inhibitors (Verapamil, Ketoconazole and Quinindine) across the rat everted gut sacs ex vivo. The present study results suggested that PGJ has both effects (inhibition, in SDS and induction, in MDS) on CYP3A4-mediated saquinavir metabolism in vivo and inhibitory effect on the P-gp mediated intestinal transport of saquinavir ex vivo. Further studies are needed to confirm this interaction at cellular level using cell lines and in humans

A Prospective study on the assessment of risk factors for type 2 diabetes mellitus in outpatients department of a south Indian tertiary care hospital: A case-control study

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.Â