Prasad Neerati, Ravi Karan M and Jagat R Kanwar
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 (Tmax) 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.