Pharmacokinetic/pharmacodynamic modeling for the determination of a cimicoxib dosing regimen in the dog

BMC Veterinary Research

Table 3 Pharmacodynamics parameters describing the cimicoxib effect after an oral administration of cimicoxib (2 mg/kg) in 4 poor metabolizers (PM) and 8 extensive metabolizers (EM) dogs

	EC₅₀or IC₅₀(ng/mL)		Emax (no unit)		Imax (no unit)		Kin (°C.h^-1or m.s^-1.h^-1or score.h^-1or normalised force.h^-1)		Kout (h^-1)		n (no unit)
	PM	EM	PM	EM	PM	EM	PM	EM	PM	EM	PM	EM
Body temperature (°C)	473.4 [422.7, 558.9]	193.2 [95.9, 330.0]	0.04 [0.03, 0.04]	0.04 [0.03, 0.06]	N.A	N.A	45.84 [42.76, 49.19]	41.30 [20.76, 84.13]	1.17 [1.09, 1.25]	1.04 [0.53, 2.10]	6.99 [1.99, 10.00]	5.09 [1.31, 10.00]
Creeping speed (m/s)	344.5 [140.0, 592.7]	239.4 [136.0, 427.5]	N.A	N.A	0.70 [0.44, 0.87]	0.71 [0.38, 1.00]	0.76 [0.36, 0.97]	0.90 [0.15, 2.71]	1.07 [0.80, 1.47]	0.95 [0.24, 2.02]	3.68 [0.49, 10.00]	4.74 [0.71, 10.00]
Lameness score (no unit)	785.8 [579.4, 916.1]	284.3 [71.1, 827.8]	N.A	N.A	Fixed at 1	Fixed at 1	2.57 [0.70, 4.96]	5.34 [1.17, 16.87]	0.509 [0.14, 0.99]	1.08 [0.22, 3.54]	2.70 [0.66, 5.03]	4.25 [1.12, 10.00]
Vertical force (no unit)	325.1 [235.3, 397.6]	160.8 [51.4, 339.3]	N.A	N.A	0.97 [0.95, 0.99]	0.98 [0.93, 1.00]	0.09 [0.07, 0.10]	0.09 [0.06, 0.10]	8.47 [5.09, 9.99]	7.40 [3.21, 10.00]	5.67 [4.21, 6.67]	6.13 [2.13, 9.73]

Parameters were estimated using indirect effect PK/PD models. Mean and range, Emax: maximum effect, EC₅₀: plasma concentration to obtain 50% of the Emax, IC₅₀: plasma concentration to obtain 50% of the Imax, Kin: the zero-order rate constant for the production of the response; Kout: the first-order rate constant for the loss of the response; n: coefficient of Hill that measures the slope of the concentration-effect relationship; N.A.: Not Applicable.

ISSN: 1746-6148