TABLE 4.

Perturbed writhing PK/PD model parameters

(a) Additivity
Combination model—pure additivity
Trazodone					Gabapentin
Parameter	Units	Estimate	%CV	%SE	Parameter	Units	Estimate	%CV	%SE
k 2	L/μmoles/min	12.7		28.4	k 2	L/μmoles/min	0.0808		26.7
Interindividual variability					Interindividual variability
${\overline{\omega }}_{k_2}^2$		1.43	119.6	28.4	${\overline{\omega }}_{k_2}^2$		1.67	129.2	28.2
Intra‐individual variability					OBJF = 1455.14
${\sigma }_{\mathrm{add}}^2$		2.62		13.1

(b) Synergism
Combination model—interaction
Trazodone					Gabapentin
Parameter	Units	Estimate	%CV	%SE	Parameter	Units	Estimate	%CV	%SE
k 2	L/μmoles/min	10.9		23.4	k 2	L/μmoles/min	0.0490		32.4
Interindividual variance					Interindividual variance
${\overline{\omega }}_{k_2}^2$		1.42	119.2	27.7	${\overline{\omega }}_{k_2}^2$		1.78	133.4	26.4
Combination Index
Γ		16.0		24.4
Intra‐individual variability					OBJF = 1438.13
${\sigma }_{\mathrm{add}}^2$		2.64		13.0

Note: Analyses testing additive (panel A) and synergic (panel B) effects at the doses of trazodone‐gabapentin of 0.075–1.5, 0.15–1.5 mg/kg, respectively.

Abbreviations: %CV, percent coefficient of variation; %SE, percent standard error; k ₂, potency parameter; PK/PD, pharmacokinetic/pharmacodynamic; ω, interindividual variability; γ, combination index; σ, intra‐individual variability.