Table 1.

PK/PD model parameters

Model	Parameter	Symbol	Unit	Value	RSE (%)	IIV (%)	RSE IIV (%)
PK AZD9567	Lag time	$t_{\text{lag}}$	h	0.183	2	12a	14a
	Absorption rate constant	$k_{\mathrm{a}0}$	h−1	38.2	32	72a	8a
	Relative bioavailability	$F$		1b		20	9
	Central volume of distribution	$V_{\mathrm{c}}$	L	26.8	4
	Intercompartment clearance	$Q$	L h−1	0.500	8
	Peripheral volume of distribution	$V_{\mathrm{p}}$	L	392	13	108	17
	Clearance	$\text{CL}$	L h−1	3.70	6	27	9
	Covariate model (dose on $F$)	$s$	mg−1	0.00253	12
	Covariate model (dose on $k_{\mathrm{a}}$)	$\mathrm{\lambda }$		0.103	32
	Covariate model (dose on $k_{\mathrm{a}}$)	$\alpha$	mg−1	0.0592	19
	Residual error	$\sigma$	%	10.9	5
PK prednisolone	No. of transit compartments	$n$		8.11	12	61	15
	Mean transit time	$t_{\mathrm{m}}$	h	0.772	7	41	10
	Relative bioavailability	$F$		1b		17	15
	Central volume of distribution	$V_{\mathrm{c}}$	L	352	5
	Inter‐compartment clearance	$Q$	L h−1	5.81	50
	Peripheral volume of distribution	$V_{\mathrm{p}}$	L	23.6	32
	Clearance	$\text{CL}$	L h−1	110	3	12	12
	Residual error	$\sigma$	%	35.5	7
PK/PD TNFα	Baseline TNFα	$E_0$	ng/L	28.6 × 103	4	36	8
	Transduction rate constant	$k_{\mathrm{t}}$	h−1	0.308	12
	Weighting parameter	$w$		0.216	12
	Maximal inhibition, AZD9567	${\mathrm{I}}_{max}$		1b
	Concentration for half‐maximal effect, total AZD9567	${\text{IC}}_{50}$	nM	765	10	46	16
	Concentration for half‐maximal effect, unbound AZD9567	${\text{IC}}_{50}$	nM	4.87c
	Sigmoidicity parameter, AZD9567	$\gamma$		1.40	7
	Maximal inhibition, prednisolone	${\mathrm{I}}_{max}$		1b
	Concentration for half‐maximal effect, unbound prednisolone	${\text{IC}}_{50}$	nM	17.0	10	16	33
	Sigmoidicity parameter, prednisolone	$\gamma$		1.33	7
	Residual error	$\sigma$	%	44.5	5

Reporting of percent IIV, IOV, and residual error was done using the approximation $100\sqrt{{·}^2}$.

IIV, interindividual variability; IOV, interoccasion variability; PD, pharmacodynamic; PK, pharmacokinetic; RSE, relative standard error.

^aThe IIV and RSE IIV columns are used for IOV for t _lag and k _a0.

^bFixed, not estimated.

^cDerived from the estimate of IC₅₀ for total AZD9567 concentrations using an unbound fraction of 0.637%.