Revisiting atenolol as a low passive permeability marker

Table 1 Parameter estimates of the S-atenolol pharmacokinetic model in rats

Parameter	Unit	Estimate	RSE (%)	IIV (%)	RSE IIV (%)
REC_blood	%	49.9	3.5	12.2	24.8
REC_brain	%	6.73	9.5	27.9	17.2
CL	mL/min	10.2	2.4	7.5	16.9
V₁	mL	215	10.8	30.3	28.4
Q	mL/min	5.56	8.9
V₂	mL	402	4.8
f_u,p		1.0	Fixed
Q_AV	mL/min	15.4	9.2
CL_in	µL/min/gbrain	17.0	48.8	134.2	27.5
K_p,uu,brain		0.040	11.3	35.5	18.0
V_u,brain	mL/g brain	0.686	Fixed
σ_{proportional,RECbrain}		0.028	9.4
σ_{additive,RECblood}	ng/mL	7.83	5.1
σ_{proportional,plasma}		0.184	20.3
σ_{proportional,blood}		0.112	8.8
σ_{proportional,brain}		0.0741	12.3
σ_{additive,brain}	ng/mL	0.22	20.2

RSE relative standard error; IIV Inter-individual variation expressed as coefficient of variation; REC relative recoveries; CL systemic total clearance; V ₁ volume of distribution of total arterial and venous compartments; Q clearance between arterial and peripheral compartments; V ₂ volume of distribution of the peripheral compartment; f _u,p unbound fraction in plasma; Q _AV clearance between arterial and venous compartments; Cl _in influx clearance into brain; K _p,uu,brain unbound partition coefficient in brain; V _u,brain unbound volume of distribution in brain; σ variances of the proportional or additive residual errors

ISSN: 2045-8118