TABLE 5

Effects of miR-34a on the PK parameters of individual drugs and metabolites

Data were fit to a noncompartmental PK model. Values represent means ± S.D. generated from six mice.

	Treatment	C_max^{^a}	AUC_0→∞^{^b}	Extrap	t_1/2	CL/F	V_z/F
				%	h	l/h	liters
Substrate
MDZ	Control	15.9 ± 8.9	23.4 ± 7.5	20.54	1.237 ± 0.710	6.995 ± 4.317	3.822 ± 1.115
	miR-34a	20.7 ± 3.0	37.4 ± 5.4^*	17.72	1.182 ± 0.245	4.122 ± 0.897	2.432 ± 0.351
PHE	Control	229.0 ± 68.2	74.3 ± 14.6	13.27	0.256 ± 0.068	2.349 ± 0.981	6.243 ± 1.295
	miR-34a	225.7 ± 96.8	91.3 ± 13.8**	14.95	0.297 ± 0.044	2.166 ± 0.461	5.032 ± 0.708
DXM	Control	247.6 ± 88.1	906.6 ± 388.7	37.30	3.052 ± 2.771	70.33 ± 20.04	23.56 ± 14.11
	miR-34a	349.2 ± 74.8^*	1276 ± 296***	49.15	2.762 ± 0.984	50.63 ± 11.41	13.81 ± 4.80
DIC	Control	841.0 ± 174.5	2.345 ± 1.768	30.09	1.832 ± 1.588	7.630 ± 5.150	5.067 ± 4.019
	miR-34a	1.448 ± 0.239^*	2.612 ± 0.752	25.69	1.558 ± 0.480	4.094 ± 1.725	2.026 ± 1.058
CLZ	Control	9.856 ± 2.443	8.722 ± 1.248	4.16	0.644 ± 0.158	6.751 ± 3.613	8.152 ± 6.015
	miR-34a	10.73 ± 1.866	11.14 ± 1.80***	5.56	0.659 ± 0.153	4.328 ± 2.053	5.089 ± 3.450
Metabolite
1′-OH-MDZ	Control	2.665 ± 0.566	7.807 ± 3.186	29.44	1.432 ± 0.553
	miR-34a	2.443 ± 0.377	7.424 ± 1.275	32.67	1.630 ± 0.249
APAP	Control	2.147 ± 0.395	1.797 ± 0.336	5.08	0.763 ± 0.265
	miR-34a	1.700 ± 0.169**	1.640 ± 0.158	4.86	0.692 ± 0.154
DXO	Control	175.6 ± 48.8	307.9 ± 41.7	22.18	1.271 ± 0.160
	miR-34a	163.2 ± 16.7	358.9 ± 51.8	25.66	1.417 ± 0.144
4′-OH-DIC	Control	136.5 ± 51.4	275.6 ± 105.8	20.94	1.286 ± 0.372
	miR-34a	126.0 ± 48.9	284.5 ± 127.1	33.77	1.984 ± 0.656
6-OH-CLZ	Control	45.57 ± 0.02	42.2 ± 11.6	25.77	0.629 ± 0.352
	miR-34a	47.50 ± 0.01	40.0 ± 5.5	17.75	0.684 ± 0.150

Extrap, extrapolated contribution to AUC.
↵^a Values are given in nM for MDZ, PHE, DXM, DIC (control), DXO, 4′-OH-DIC, and 6-OH-CLZ and in µM for DIC (miR-34a), CLZ, 1′-OH-MDZ, and APAP.
↵^b Values are given in nM·h for MDZ, PHE, DXM, DXO, 4′-OH-DIC, and 6-OH-CLZ and in µM·h for DIC, CLZ, 1′-OH-MDZ, and APAP.
↵* P < 0.001; **P < 0.01; ***P < 0.05 compared with the control (one-way analysis of variance with paired Bonferroni post hoc tests).