Influence of curcumin on the pharmacodynamics and pharmacokinetics of gliclazide in animal models

Figures & data

Table 1 Mean percent blood glucose reduction of gliclazide in presence and absence of curcumin in normal rats (n=6)

Time (h)	Gliclazide	Curcumin	Gliclazide + curcumin (SDT)	Gliclazide + curcumin (MDT)
1	31.51±1.69	−8.63±1.93	31.08±1.51	32.34±2.31
2	41.66±1.70	−3.34±1.24	40.41±1.49	42.36±2.20
3	28.98±2.04	1.40±1.29	29.01±4.44	35.44±2.96*
4	23.46±2.65	3.32±2.40	23.60±1.35	33.75±1.73*
6	30.22±2.19	5.45±1.81	30.19±4.33	36.69±1.25*
8	39.49±1.82	4.73±2.34	39.24±1.37	42.04±2.42*
10	24.24±2.40	3.15±2.79	25.97±3.65	33.39±2.22*
12	18.83±2.17	6.16±2.33	17.15±2.17	23.38±2.16*

Notes: Data expressed as mean ± standard deviation.

* Statistically significant when compared with gliclazide control.

Abbreviations: MDT, multiple-dose treatment; SDT, single-dose treatment.

Table 2 Mean percent blood glucose reduction of gliclazide in presence and absence of curcumin in diabetic rats (n=6)

Time (h)	Gliclazide	Curcumin	Gliclazide + curcumin (SDT)	Gliclazide + curcumin (MDT)
1	30.84±2.08	1.08±0.60	31.98±1.21	30.33±1.45
2	43.17±0.90	1.46±1.63	43.54±0.84	42.27±2.07
3	31.90±1.86	0.61±2.05	32.35±1.55	36.07±2.06*
4	26.53±2.25	2.46±2.56	26.47±1.81	37.62±1.65*
6	35.53±2.74	5.15±1.99	34.02±1.76	39.17±1.80*
8	40.91±1.56	6.04±1.90	42.12±1.55	41.56±1.50
10	27.95±1.32	4.14±0.97	27.44±1.43	32.64±2.30*
12	24.50±1.00	3.55±2.19	23.47±3.91	27.63±1.00*

Notes: Data expressed as mean ± standard deviation.

* Statistically significant when compared with gliclazide control.

Abbreviations: MDT, multiple-dose treatment; SDT, single-dose treatment.

Table 3 Mean percent blood glucose reduction of gliclazide in presence and absence of curcumin in rabbits (n=6)

Time (h)	Gliclazide	Curcumin	Gliclazide + curcumin (SDT)	Gliclazide + curcumin (MDT)
1	18.75±2.02	−0.5 2.46	18.11±1.41	19.11±1.96
2	29.39±3.74	1.59±1.13	29.09±0.88	29.46±2.84
3	34.10±1.90	−0.36±1.08	34.48±1.17	37.88±1.30*
4	26.15±1.94	3.48±2.80	26.47±0.82	29.12±2.15*
6	23.10±2.98	4.20±1.28	23.32±1.29	26.51±3.14*
8	17.16±1.36	9.63±3.67	17.75±1.43	23.31±2.13*
10	15.00±3.12	5.26±1.61	15.66±1.34	19.13±1.96*
12	10.65±1.03	10.68±2.22	10.45±0.79	16.50±1.51*

Notes: Data expressed as mean ± standard deviation.

* Statistically significant when compared with gliclazide control.

Abbreviations: MDT, multiple-dose treatment; SDT, single-dose treatment.

Table 4 Effect of curcumin on glucose insulin homeostasis of gliclazide in normal rats (n=6)

Parameter	Insulin (µIU/mL)		Insulin resistancea		β-cell functiona
	2 h	8 h	2 h	8 h	2 h	8 h
Gliclazide	12.21±0.45	11.76±0.20	29.70±2.40	29.61±1.08	477.81±15.61	442.79±17.85
Curcumin	7.85±0.76	7.65±0.42	34.13±3.26	30.63±1.71	166.50±16.67	176.47±10.38
Gliclazide + curcumin (SDT)	12.33±0.67	11.80±0.20	32.06±2.03	31.28±0.95	448.76±27.67	421.00±23.44
Gliclazide + curcumin (MDT)	12.09±0.21	11.54±0.52	29.82±1.06	28.64±2.09	465.16±14.11	441.40±24.00

Notes: Data expressed as mean ± standard deviation.

a Calculated by homeostasis model assessment.

Abbreviations: MDT, multiple-dose treatment; SDT, single-dose treatment.

Table 5 Effect of curcumin on glucose insulin homeostasis of gliclazide in diabetic rats (n=6)

Parameter	Insulin (µIU/mL)		Insulin resistancea		β-cell functiona
	2 h	8 h	2 h	8 h	2 h	8 h
Gliclazide	14.13±0.32	12.58±0.75	89.78±1.67	83.14±5.74	202.68±7.61	173.29±9.67
Curcumin	7.21±0.29	6.86±0.31	82.41±4.84	76.87±3.33	56.82±1.76	55.19±2.76
Gliclazide + curcumin (SDT)	14.31±0.51	12.32±0.71	97.43±3.81	85.98±5.15	191.26±6.73	160.64±10.14
Gliclazide + Ccrcumin (MDT)	14.26±0.42	13.41±0.49	94.44±4.76	90.05±3.32	195.99±4.92	181.66±8.46

Notes: Data expressed as mean ± SD.

a Calculated by homeostasis model assessment.

Abbreviations: MDT, multiple-dose treatment; SD, standard deviation; SDT, single-dose treatment.

Table 6 Effect of curcumin on glucose insulin homeostasis of gliclazide in rabbits (n=6)

Parameter	Insulin (µIU/mL)	Insulin resistancea	β-cell functiona
	3 h	3 h	3 h
Gliclazide	20.77±0.76	56.14±2.53	724.74±31.96
Curcumin	8.94±0.30	37.87±1.67	194.60±5.63
Gliclazide + curcumin (SDT)	22.39±1.19	63.38±4.06	756.90±37.40
Gliclazide + curcumin (MDT)	20.73±0.87	54.36±2.55	747.06±31.83

Notes: Data expressed as mean ± standard deviation.

a Calculated by homeostasis model assessment.

Abbreviations: MDT, multiple-dose treatment; SD, standard deviation; SDT, single-dose treatment.

Figure 1 Mean gliclazide concentration in serum (ng/mL) before and after treatment with curcumin in rabbits (n=6).

Abbreviations: MDT, multiple-dose treatment; SDT, single-dose treatment.

Table 7 Mean pharmacokinetic parameters of gliclazide before and after administration of curcumin in rabbits (n=6)

Pharmacokinetic parameter	Gliclazide	Gliclazide + curcumin (SDT)	Gliclazide + curcumin (MDT)
Cmax (ng/mL)	363.01±6.09	364.19±8.63	369.46±4.36
Tmax (h)	3.00±0.00	3.00±0.00	3.00±0.00
AUClast (h ng/mL)	3,959±14.66	3,967.76±48.07	4,062.62±26.14
AUCinf (h ng/mL)	4,954.11±38.14	5,008.30±102.22	4,963.64±88.77
AUMClast (h ng/mL)	37,998.28±144.77	38,278.83±628.45	39,218.32±292.54
AUMCinf (h ng/mL)	76,368.86±1,676.56	78,861.19±3,792.62	72,887.66±4,837.15
T1/2 (h)	10.11±0.16	10.38±0.31	9.19±0.87
Kel (1/h)	0.07±0.00	0.07±0.00	0.08±0.01
MRT (h)	9.60±0.01	9.65±0.06	9.65±0.02
CL (L/h)	0.07±0.00	0.07±0.00	0.08±0.01

Note: Data expressed as mean ± standard deviation.

Abbreviations: AUC, area under the concentration time curve; AUMC, area under first moment curve; CL, clearance; C_max, peak serum concentration; K_el: elimination rate constant; MDT, multiple-dose treatment; MRT, mean residence time; SD, standard deviation; SDT, single-dose treatment; T_max, peak time; T_1/2, terminal half-life.