. 2013 Apr;41(4):801–813. doi: 10.1124/dmd.112.050161

TABLE 5.

Summary of clonidine drug-dependent parameters

Parameter	Value	Methods/Reference
Molecular weight	230.1	^a
Log P_o:w	1.57	^b
pKa	8.05	^c
B/P ratio	1.012	^d
f_u,_p	0.48	^e
F_a	0.98	Calculated ^f
k_a (h⁻¹)	1.0	Optimized in the range of 1.0–2.3 ^g
F_g	0.99	Predicted by Q_gut
V_ss (l/kg)	2.55	Predicted ^h
CL_IV (l/h)	13.6	ⁱ
CL_r (l/h)	7.0	^j
CL_int,u (µl/min/pmol of isoform)		^k


CL_int,u,2D6	0.32
CL_int,u,3A	0.006
CL_int,u,1A2	0.008
f_m and f_e (2D6 EM) (%)		^e, ^l
f_m and f_e (2D6 EM) (%)
f_m,2D6	33
f_m,3A	11
f_m,1A2	5
f_e	51

Q_gut, hybrid parameter of blood flow and drug permeability; V_ss, volume of distribution at steady state.

^{^a}

Hardman et al. (2001).

^{^b}

Reported in Ghasemi and Saaidpour (2007).

^{^c}

Reported in Cody and DeTitta (1979).

^{^d}

Predicted using physicochemical parameters in Simcyp. Reported B/P ratio in rodents is 1.07 (Yamahata et al., 1996).

^{^e}

Reported in Vanholder et al. (1988) and Boehringer Ingelheim (2011).

^{^f}

Mean reported bioavailability is 92% (range 88–96%) following a single oral dose of clonidine (Frisk-Holmberg et al., 1981; Arndts et al., 1983). Simcyp-predicted F_h is 0.95 and F_g is 0.99, therefore calculated F_a is 0.98.

^{^g}

Reported in Frisk-Holmberg et al. (1981); Anavekar et al. (1982); and Porchet et al. (1992).

^{^h}

Predicted according to Rodgers and Rowland (2007); estimated V_ss value from i.v. dosing profiles is ∼3 l/kg (Frisk-Holmberg et al., 1981). Mean K_p values determined in rodents (Conway and Jarrott, 1980; Yamahata et al., 1996) were used, as opposed to predicted K_p values, because these values were found to better characterize the biphasic distribution of clonidine in plasma following either i.v. or oral dosing.

^ⁱ

Mean of reported values (Frisk-Holmberg et al., 1981; Arndts et al., 1983).

^{^j}

Calculated by taking the product of CL_IV and reported mean f_e (Frisk-Holmberg et al., 1981; Arndts et al., 1983; Buchanan et al., 2009).

^{^k}

Back calculation from hepatic CL (CL - CL_r), f_m for individual P450 (see next footnote), and average population values for liver weight and hepatic P450 enzyme abundance of 137, 52, and 8 pmol/mg protein for CYP3A, 1A2, and 2D6, respectively.

^{^l}

Reported f_m for individual P450 was calculated by taking the product of f_m (i.e., 1 - f_e) and the contribution from individual CYPs (67, 22, and 11% for 2D6, 3A, and 1A2, respectively) obtained in human liver microsomes (Claessens et al., 2010).