TABLE 3

Effect of microsomal protein concentration and binding on triazolam, diazepam, and clonazepam in vitro CL_int in rat microsomes

Values are mean ± S.D. (n = 4). CL_int is expressed as μl/min/mg, and CL_int values represent those obtained from monoexponential fits in all cases.

Protein concentration (mg/ml)	Triazolam					Diazepam
Protein concentration (mg/ml)		CL_int	f_u	CL_{int (u)}	CL_int	f_u	CL_{int (u)}	CL_int	f_u	CL_{int (u)}
0.1	230 ± 80	0.98	240 ± 81
0.5	230 ± 35	0.91	250 ± 38	210 ± 60	0.93	250 ± 72	81 ± 7.9	0.86	94 ± 9.1^a
1	190 ± 25	0.84	230 ± 30		0.88		74 ± 7.4	0.76	97 ± 9.7^a
2	160 ± 26	0.72	220 ± 35^a		0.78		52 ± 5.5	0.61	86 ± 9.0^a,^b
5	93 ± 20	0.51	180 ± 40^a,^b	73 ± 23	0.58	210 ± 67^a,^b	23 ± 2.6	0.38	61 ± 6.8^a,^b

↵ a The biexponential model gave the best model fit (according to the AIC); however, only the monoexponential estimate is shown (where the 1/y weighting resulted in emphasis on the first phase of the profile. N.B.: Use of only the initial phase in the fitting had no impact on the CL_int prediction).
↵ b Significantly different from the lowest microsomal protein concentration for unbound CL_int values only (p < 0.05, Dunnett's test for triazolam and clonazepam and two-way ANOVA for diazepam).