TABLE 2

Calculated total (K_p,brain) and unbound (K_p,uu,brain) brain- and unbound CSF (K_p,uu,CSF)-to-plasma ratios

	Internal Compounds				Commercial Compounds
	A	B	C	D	Atenolol	Loperamide	Minoxidil	NFPS	Sulpiride
K_p,brain
1 mg/kg over 4 h	0.49 ± 0.14	0.23 ± 0.06	0.30 ± 0.05	3.11 ± 0.44	0.08 ± 0.01	0.15 ± 0.03	0.14 ± 0.03	0.33 ± 0.04	0.11 ± 0.01
1 mg/kg over 24 h	0.72 ± 0.12	0.21 ± 0.07	0.47 ± 0.05	4.04 ± 0.68	0.09 ± 0.01	0.10 ± 0.02	0.29 ± 0.17	1.01 ± 0.38^*	0.18 ± 0.01
6 mg/kg over 24 h	0.81 ± 0.14	0.28 ± 0.06	0.51 ± 0.10^*	3.73 ± 0.54	0.09 ± 0.02	0.15 ± 0.04	0.19 ± 0.08	0.74 ± 0.18	0.19 ± 0.05^*
K_p,uu.brain^a
1 mg/kg over 4 h	0.80 ± 0.23	0.10 ± 0.03	0.24 ± 0.04	0.47 ± 0.07	0.05 ± 0.01	0.004 ± 0.001	0.14 ± 0.03	0.014 ± 0.001	0.044 ± 0.003
1 mg/kg over 24 h	1.17 ± 0.20	0.09 ± 0.03	0.38 ± 0.04	0.61 ± 0.10	0.06 ± 0.004	0.003 ± 0.001	0.29 ± 0.17	0.04 ± 0.02^*	0.072 ± 0.005^*
6 mg/kg over 24 h	1.32 ± 0.23	0.12 ± 0.03	0.41 ± 0.08^*	0.56 ± 0.08	0.06 ± 0.01	0.004 ± 0.001	0.20 ± 0.09	0.03 ± 0.01	0.076 ± 0.021^*
K_p,uu,CSF^b
1 mg/kg over 4 h	N.A.	N.A.	N.A.	N.A.	0.094 ± 0.044	0.318 ± 0.143	0.14 ± 0.02	0.253 ± 0.088	0.099 ± 0.001
1 mg/kg over 24 h	N.A.	N.A.	N.A.	N.A.	0.091 ± 0.058	0.451^c	0.17^c	0.412^c	0.13 ± 0.07
6 mg/kg over 24 h	N.A.	N.A.	N.A.	N.A.	0.081 ± 0.018	0.126^c	0.16 ± 0.05	0.169 ± 0.057	0.12 ± 0.01

N.A., not available because CSF samples were not collected; N.C., not calculated because drug conc. in CSF was not detectable.
↵^a Unbound brain-to-plasma ratio was calculated using eq. 3, and unbound fractions in plasma and brain were shown in Table 1.
↵^b CSF-to-unbound plasma ratio was calculated using eq. 4, and unbound fractions in plasma and CSF were shown in Table 1.
↵^c S.D. was not available, since the sample size was fewer than 3.
↵^* P < 0.05 compared with 1 mg/kg infusion over 4 h.