Background: Curcumin is the principal curcuminoid of the popular Indian spice ingredients commonly known as turmeric. Curcumin is reported to inhibit cytochrome P-450 (CYP) enzymes and its isozymes. As turmeric is being consumed every day in Indian spices, it is essential to determine the potential interaction with drugs metabolised by CYP3A4 system. Methods and results: The study was conducted to determine the potential influence of curcumin on pharmacokinetics and pharmacodynamics of pioglitazone in normal and diabetic rat models. In first study, three groups (groups 1, 2 and 3; n=6) of rats were taken as non diabetic (normal) groups. Second study, three other groups: (groups 4, 5 and 6) were selected similarly to test the effects on diabetic group after receiving alloxan monohydrate (120 mg/kg). Group 1 and 2; group 4 and 5 received pioglitazone orally (10 mg/kg) and curcumin (60 mg/kg), respectively. Groups 3 and 6 were tested for single dose and multiple dose interaction effects on non diabetic and diabetic rats with curcumin for single day and for eight days, respectively. By the end of curcumin pre-treatment pioglitazone was given on the eighth day. Blood samples (0.8 ml) were collected via retro orbital plexus, at the time intervals of 0, 0.5, 1, 2, 4, 8 and 24 hours and double the volume of sample is replaced with normal saline intra peritoneally to maintain the body fluid in animals and PK and PD parameters were measured. Curcumin significantly increased the area under plasma concentration time curve (AUC) and area under the movement curve (AUMC) of pioglitazone in both normal and diabetic rats. There was a significant decrease in maximum observed plasma concentration (T max) in both normal and diabetic rats. Conclusion: Curcumin significantly decreased the metabolism of pioglitazone and, the combination has more beneficial effect in diabetes and warrants dose adjustment of pioglitazone in diabetic models.
The purpose of the present study was to assess the effect of resveratrol (RSV) on the pharmacokinetics of naproxen (NAP) in rats. A single dose of RSV 30mg/kg was administered once during treatment phase. A single dose of NAP 25mg/kg was administered after RSV treatment. The blood samples were collected after NAP dosing at predetermined time intervals and analyzed by HPLC. In comparison with the control, RSV pretreatment significantly enhanced maximum plasma concentration (Cmax), area under the curve (AUC), and half life (t1/2) and significantly decreased apparent oral clearance (CL/F) and apparent volume of distribution (Vd/F), while there was no significant change observed in time to reach maximum concentration (tmax) of NAP. The results suggest that the altered pharmacokinetics of NAP might be attributed to RSV-mediated inhibition of CYP1A2 enzyme. Therefore, combination therapy of NAP along with RSV may represent a novel approach to reduce dosage and results in reduced gastrointestinal side effects of NAP.
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