Stereoselective propranolol metabolism in two drug induced rat hepatic microsomes

Table 1 Accuracy and precision to assay propranolol in rat liver microsome

Target concentrations (μmol/L)	Recovery (%)	Precisions (RSD, %)
		Intra-assay (n = 3)	Inter-assay (n = 3)
60	98.8	5.1	5.6
1 2 0	99.5	3.5	4.8
240	101.0	3.2	5.3

Table 2 Ratio of R( + )/S( - ) propranolol concentration in incubation m edia at different incubation time

Group	Ratio of R( + )/S( - ) propranolol
	0	5	10	15	20	30 (min)
Control	0.989	9.99 ± 0.07	1.01 ± 0.10	1.02 ± 0.02	1.04 ± 0.04	1.07 ± 0.02
BNF	0.989	0.94 ± 0.05	0.93 ± 0.06	0.93 ± 0.04a	0.95 ± 0.05c	0.91 ± 0.05bc
PB	0.989	1.05 ± 0.06	1.04 ± 0.08	1.05 ± 0.10	1.09 ± 0.05	1.09 ± 0.06

Values were obtained from propranolol concentration at 120 μmol/L for each enantiomer, BNF and PB: microsomes from the rats induced with BNF (β-naphthoflavone) or (phenobarbital) 80 mg/(kg·d), ip, 3 d, respectively. ^-x ± s, n = 3.

^aP < 0.05,

^bP < 0.01, compared with control;

^cP < 0.05, compared with PB by unpaired t test.

Table 3 Enzymatic kinetic parameters in propranolol enantiomer metab olism in vitro in rat hepatic microsomes induced by β-naphthoflavone or ph enobarbital

Group	Enantiomer	Km μmol/L	Vmax mmol/g/min	Clint L/min/g protein	R( + )Vmax: S( - )Vmax
Control	R( + )	30 ± 8	1.5 ± 0.2b	60 ± 3b	0.5
	S( - )	18 ± 5	2.9 ± 0.3	170 ± 30
BNF	R( + )	34 ± 3	3.8 ± 0.3fh	111.0 ± 1afh	1.14
	S( - )	39 ± 7d	3.3 ± 0.5g	84 ± 5eh
P B	R( + )	38 ± 17	0.07 ± 0.03ef	2.0 ± 2cf	0.038
	S( - )	36 ± 10d	1.94 ± 0.07e	56.0 ± 1e

Clint (intrinsic clearance) is the ratio of V_max/Km, mean ± s, n = 3.

^aP < 0.05,

^bP < 0.01,

^cP < 0.001, compared with S( - ) propranolol;

^dP < 0.05,

^eP < 0.01,

^fP < 0.001, compared with corresponding enantiomer in control group;

^gP < 0.01,

^hP < 0.001, compared with corresponding enantiome r in PB group with unpaired t test.