Table 2.

Rate constant parameters of drugs investigated in previous human drug interaction studies

Drugs	Dosing interval (time before administration of AST-120)	k d1.2 (10−4·s−1)	k d6.8 (10−4·s−1)	T lagd (h)	R d (%)	k a (h−1)	T laga (h)	R a (%)
Amlodipine	Simultaneous	25.54	3.99	0.00	14.2	0.62	0.00	1.0
	30 min				99.0			26.8
	90 min				100.0			60.8
	240 min				100.0			91.8
Aspirin, dihydroxyaluminum aminoacetate, magnesium carbonate (Bufferin combination tablet)	Simultaneous	11.00	27.64	0.00	15.3	1.55	0.00	2.6
	60 min				100.0			78.8
Losartan	30 min	0.6	10.5	0.00	84.8	1.43	0.33	21.7
	60 min				97.7			61.6
Metoprolol ER	Simultaneous	1.03	0.76	0.00	0.6	0.11	0.00	0.2
	60 min				30.9			10.7
Nifedipine	Simultaneous	17.59	11.58	0.00	10.0	2.49	0.28	0.0
	30 min				95.8			41.6
	120 min				99.8			98.6
Triazolam	Simultaneous	14.69	11.08	0.00	8.4	17.34	0.44	0.0

Using the Noyes-Whitney formula, k _d1.2 (dissolution rate constant for the first fluid for the dissolution test, pH 1.2) and k_d6.8 (dissolution rate constant for the second fluid for the dissolution test, pH 6.8) were calculated. The higher value was used for the prediction. T _lagd (lag time to 1 % dissolution) and R _d. (dissolution rate at each dosing interval between AST-120 and concomitant drug administration) were calculated. When AST-120 and the concomitantly administered drug were administered simultaneously, the time interval was set as 1 min for the calculation

k _a (absorption rate constant), T _laga (lag time in absorption), and R _a (absorption rate compared to total absorption until the time of AST-120 administration) were calculated using the better-fitted model with WinNonlin® from visual inspection