Effect of transporter inhibition on the distribution of cefadroxil in rat brain

Table 1 Pharmacokinetic parameters of unbound cefadroxil in rat blood and brain on Day 1 (Control, Ctrl) and Day 2 (with probenecid, Pro)

Parameters	Unit	Day 1 (Ctrl)	Day 2 (Pro)	Pro/Ctrl
Blood
AUC_u (0–420)	μg*min/mL	1747 ± 90	2801 ± 175***	1.60
AUC_u (0-inf)	μg*min/mL	1802 ± 97	2873 ± 177***	1.59
C_u,ss,blood	μg/mL	8.5 ± 0.4	13.8 ± 0.9***	1.62
MRT_iv	min	71 ± 4	77 ± 4	1.05
t_1/2	min	49 ± 2	53 ± 3	1.09
CL	mL/min/kg	16.9 ± 1.0	10.7 ± 0.7***	0.63
V_ss	L/kg	1.19 ± 0.12	0.82 ± 0.10***	0.69
Brain ECF
AUC_u (0–420)	μg*min/mL	31 ± 5	122 ± 31*	3.93
AUC_u (0-inf)	μg*min/mL	40 ± 7	174 ± 35**	4.37
K_p,uu,ECF (0–420)		0.018 ± 0.003	0.042 ± 0.009*	2.35
K_p,uu,ECF (0-inf)		0.022 ± 0.003	0.058 ± 0.009*	2.63
Brain CSF
AUC_u (0–420)	μg*min/mL	39 ± 12	73 ± 27	1.88
AUC_u (0-inf)	μg*min/mL	57 ± 15	117 ± 50	2.04
K_p,uu,CSF (0–420)		0.022 ± 0.006	0.024 ± 0.008	1.13
K_p,uu,CSF (0-inf)		0.031 ± 0.007	0.039 ± 0.015	1.26

Data are expressed as mean ± SEM (n = 6). A paired t-test was performed to compare cefadroxil parameters between the control (without probenecid) and treatment (with probenecid) phases of the study. *p < 0.05, **p < 0.01, and ***p < 0.001. Abbreviations: AUC_u, Area under the unbound concentration-time curve from time zero to 420 min (0–420) or from time zero to infinity (0-inf); C_u,ss,blood, Unbound steady-state blood concentration; MRT_iv, Mean residence time; t_1/2, Half-life; CL, Total clearance; V_ss, Volume of distribution steady-state; K_p,uu,ECF, Ratio of AUC_u in brain ECF to AUC_u in blood; and K_p,uu,CSF, Ratio of AUC_u in CSF to AUC_u in blood.

ISSN: 2045-8118