CORRECTION TO “Influence of Cremophor EL and Genetic Polymorphisms on the Pharmacokinetics of Paclitaxel and Its Metabolites Using a Mechanism-Based Model”

doi:10.1124/dmd.39.3.563

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TABLE 3

Parameter estimates for the final model without covariate relations

Parameter	Estimate	RSE	LLP 95% CI		RSE/RSE Prior
Parameter	Estimate	RSE	Lower	Upper	RSE/RSE Prior
		%
CL_pac (l/h)	378	8.4	322	441
V₁ (liters)	188	11			0.66
V₂ (liters)	1100	8.2			0.54
V₃ (liters)	222	14			0.68
Q₂ (l/h)	123	10			0.45
Q₃ (l/h)	181	13			0.57
B_lin	7.89	10			0.84
B_CrEL	3.62	9.1			0.91
B_max (μmol/l)	0.0207	22			0.81
K_m (μmol/l)	0.000123	36			0.83
ε_{1, pac} (%)	24.4	4.7	22.3	26.8
IIV_{CL_pac} (CV %)^{^a}	15.3	39^{^b}	10.0	22.3
IIV_{B_lin} (CV %)^{^a}	101	34^{^b}	67.3	176
CL_6αOH/fm_pac (l/h)	2830	26	1850	4750
V_6αOH/fm_pac (liters)	1390	24	945	2230
B_{CrEL, 6αOH}	43.0	40	24.4	99
B_{nsp, 6αOH} (μmol/l)	0.000754	12	0.000588	0.000947
ε_{1, 6αOH} (%)	25.4	5.6	22.9	28.4
ε_{2, 6αOH, i=1} (μmol/l)	0.00447	30	0.00250	0.00772
IIV_{CL_6αOH/fm_pac} (CV %)^{^a}	36.6	36^{^b}	25.1	53.8
CL_p3OH/fm_pac (l/h)	1470	16	1090	2020
V_p3OH/fm_pac (l/h)	1140	13	883	1490
B_{CrEL, p3OH}	8.60	32	5.24	16.1
B_{nsp, p3OH} (μmol/l)	0.00124	10	0.00103	0.00149
ε_{1, p3OH} (%)	37.7	4.8	34.5	41.6
IIV_{fp3OH/fm_pac}	0.425^{^c}	29^{^b}	0.245^{^c}	0.769^{^c}
CrEL₅₀ (ml/l)	4.48	18	3.55	6.21
Hill_CrEL	2.71	13	2.20	3.39
IIV_{Hill_CrEL} (CV %)^{^a}	40.1	38^{^b}	26.8	58.9
CL_diOH/fm_met (l/h)	831	15	606	1140
V_diOH/fm_met (liters)	167	23	97.1	246
ε_{1, diOH} (%)	49.8	8.4	42.6	59.3
ε_{2, diOH} (μmol/l)	0.00197	22	0.00134	0.00315
IIV_{CL_diOH/fm_met} (CV %)^{^a}	60.7	39^{^b}	40.8	104

CL_pac, clearance of unbound concentrations of paclitaxel; V₁, V₂, and V₃, volumes of the central, first, and second peripheral compartment for unbound concentrations of paclitaxel; Q₂ and Q₃, intercompartmental clearances between the central and peripheral compartments for unbound concentrations of paclitaxel; B_lin, linear binding to plasma components; B_CrEL, binding directly proportional to CrEL concentration; B_max, maximal binding to plasma components; K_m, concentration at half of the maximal binding to plasma components; CL_6αOH/fm_pac and CL_p3OH/fm_pac, clearance of unbound concentrations of 6αOH-pac and p3OH-pac over fraction metabolized unbound paclitaxel; V_6αOH/fm_pac and V_p3OH/fm_pac, volume of distribution of unbound concentrations of 6αOH-pac and p3OH-pac over fraction metabolized unbound paclitaxel; B_{CrEL, 6αOH} and B_{CrEL, p3OH}, maximal binding rate to CrEL of 6αOH-pac and p3OH-pac; B_{nsp, 6αOH} and B_{nsp, p3OH}, nonspecific CrEL component for 6αOH-pac and p3OH-pac; CrEL₅₀, CrEL concentration at half-maximal binding rate; Hill_CrEL, Hill coefficient for CrEL concentration; CL_{diOH/fm_met}, clearance of unbound concentrations of diOH-pac over fraction metabolized unbound primary metabolite; V_{diOH/fm_met}, volume of distribution of unbound concentrations of diOH-pac over fraction metabolized unbound primary metabolite; ε₁, proportional residual error for total concentrations; ε_{2, 6αOH, i=1}, additive error for first sample for each individual of total concentration of 6αOH-pac; ε_{2, diOH}, additive error for total concentration of diOH-pac; IIV_{CL_pac}, IIV_Blin, IIV_{CL_6αOH/fm_pac}, IIV_{f_p3OH/fm_pac}, IIV_{Hill_CrEL}, IIV_{CL_diOH/fm_met}, interindividual variability in the designated parameter.
↵a Coefficient of variation, calculated as [exp(ω²) − 1]^0.5.
↵b With respect to the variance term, ω².
↵c Estimate given for the corresponding variance term, ω², of β in eqs. 5 and 6.