INFLUENCE OF LOVASTATIN ON PHARMACOKINETICS AND PHARMACODYNAMICS OF GLIPIZIDE IN HEALTHY AND STREPTOZOTOCIN - INDUCED DIABETIC RATS: INVOLVEMENT OF P-GLYCOPROTEIN INHIBITION

ABSTRACTThis study evaluated the effect of lovastatin (Lov) on the pharmacokinetics and pharmacodynamics of glipizide (Gpz) in healthy and streptozotocininduceddiabeticrats.In singledose study(SDS), blood samples werecollectedonthe 1st day, whereas in multiple dose study on the 15 day at0-12 hrs. Lov significantly altered the pharmacokinetic parameters at the dose of 15 mg/kg in SDS and multiple dose study. The C of Gpz wasincreased from 2.97 to 8.38 and 9.87 to 24.58 ng/mL in healthy and diabetic rats, respectively, in multiple dose study. Rat everted sacs were used tostudy the transport of Gpz in the presence of Lov and verapamil (P-glycoprotein [P-gp] inhibitor). The transport of Gpz from mucosal to the serosalsurface was significantly increased from 4.32 to 5.65 and 6.02 µg/mL in the presence of Lov and verapamil, respectively. The interaction between Lovand Gpz is due to P-gp and CYP2C9 inhibition.Keywords: Diabetes, Dyslipidemia, Glipizide, Lovastatin, P-glycoprotein.maxth

ID: 88: PHOSPHOLIPID BASED LIPOIDTM NANOEMULSION OF CURCUMIN IN LINSEED OIL SHOWED INCREASED BIOAVAILABILITY AND ASSISTS IN ELEVATING THE LEVELS OF DOCOSAHEXAENOIC ACID IN SERUM AND LIVER LIPIDS OF RATS

The present study was designed to prepare curcumin nanoemulsions using phospholipid core material (LipoidTM) and exploring the possibility of enhancing its bioavailability in rats. Curcumin was dissolved in coconut oil (MCFA rich), Sunflower oil (SNO, n-6 PUFA rich) or Linseed oil (LSO,n-3 PUFA rich) and nanoemulsions were prepared by high pressure homogenization after mixing with LipoidTM. The bioavailability of curcumin was measured in vitro by transportation through intestinal everted sacs and by in vivo method after giving curcumin emulsions to rats by intubation for 60 days. The pharmacokinetics of curcumin in lymph, serum and tissues were studied. The transportation through intestinal everted sacs by nanocurcumin in which curcumin was dissolved in SNO or LSO was increased by 79% and 437% respectively when compared to curcumin given in these oils without making nanoemulsions. In single oral dose study, the rats given 125 mg of curcumin though intubation showed the presence of curcumin in lymph reaching a maximum concentration of 19.16 mg/ml and 2.37 mg/ml at 2.5h when nanocurcumin was prepared after dissolving curcumin in LSO or SNO respectively. When curcumin was given SNO or LSO without emulsification, the amount of curcumin present in lymph was found to reach a maximum level of 4.58 mg/ml and 1.25 mg/ml respectively with a Tmax of 6h. Pharmacokinetics showed higher levels of curcumin in serum and liver of rats provided nanocurcumin in which curcumin dissolved in SNO or LSO as compared to rats given curcumin without emulsion formation. Similar trend was observed when weaning rats were given 65 mg of curcumin through intubation per day for a period of 60 days. High levels of curcumin was present in serum and liver of rats given curcumin in nanoemulsions form. A small amount of curcumin was observed in brain and heart of rats given curcumin in nanocurcumin. Higher levels of docosahexaenoic acid in serum and tissue lipids were observed in rats given curcumin with LSO in nanoemulsion form. This study indicated that bioavailability of curcumin could be increased when provided as nanoemulsion with a phospholid based core material LipoidTM and LSO.