Table 3.

Comparison between different structural pharmacodynamic models of the inhibitory effect on salivary flow of darifenacin and its hydroxylated metabolite.

Model type	Direct effect	Link	Indirect response	Binding	Binding (final model)
OFV	−305	−857	−738	−920	−981
Base (ml min−1)	1.98	1.99	1.97	2.00	2.05 ± 0.08
IIV (base) (%)	53	52	52	52	52
NTO–base					−0.102 ± 0.017
Emax (ml min−1)	0.909	1.13	1.17	1.09	1.08 ± 0.027
EC50 or KD* (nm)	19.3	33.3	36.6	28.8*	0.557 ± 0.066*
IIV (EC50) (%)	89	82	83	83	82
k (h−1)	NA	1.88	3.89	0.983	0.974 ± 0.060
T1/2k (min)	NA	22	11	42	41
Rel. potency (%)	2.86	15.1	12.8	11.1	2.09 ± 1.36†
Residual error
Additive (ml min−1)	0.332	0.254	0.256	0.248	0.257
Proportional (%)	25.9	29.5	29.7	29.6	28.9
IIV (residual) (%)	25	27	27	27	27

OFV, Objective function value; base, baseline salivary flow (SF); IIV, interindividual variability; NTO, night-time observations–effect on Base; E_max, maximum decrease in SF; EC₅₀, concentration of active moiety associated with 50% of E_max; K_D, ratio of rate constant from active to inactive receptors (k_off) over rate constant of inactive to active receptors (k_on); k, effect–delay rate constant (link-model, k_e0; indirect-effect, k_out; binding-model, k_off); T_1/2k, half-life k; Rel. potency, potency of the metabolite for decreasing SF relative to darifenacin; NA, not applicable.

^*For binding model only.

^†Corrected for free fraction.