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

BMC Veterinary Research

Table 2 Level and duration of maximum improvement for each endpoint describing the effects of the cimicoxib (2 mg/kg) administered by the oral route in the 4 Poor Metabolizers (PM) and 8 Extensive Metabolizers (EM) dogs

Endpoint	Maximum effect		Duration of the maximal effect		Total duration of the effect
	PM	EM	PM	EM	PM	EM
Body temperature	87 ± 9%	84 ± 8%	19.6 h (from 2.1 to 21.7)	7 h (from 2.1 to 9.1 h)	25 h	13 h
Paw circumference	15 ± 3%	14 ± 2%	7 h (from 4.2 to 11.2 h)	9 h (from 2.2 to 11.2 h)	20 h	15 h
Skin plantar temperature	No plateau observed	38 ± 6%	Could not be determined	7 h (from 2.3 to 9.3 h)	22 h	13 h
Creeping speed	77 ± 7%	76 ± 9%	11.1 h (from 4.2 to 15.3 h)	7 h (from 2.2 to 9.2 h)	25 h	15 h
Clinical lameness score	1 or 2	1 or 2	10.9 h (from 4.8 to 15.7 h)	8.8 h (from 2.8 to 16 h)	not assessed	not assessed
Vertical normalized force	67 ± 6%	68 ± 7%	11.1 h (from 4.5 to 15.5 h)	6.9 h (from 2.6 to 9.5 h)	28 h	16 h
Analgesia	162 ± 53%	232 ± 45%	8.8 h (from 2.9 to 11.8 h)	7 h (from 2.9 to 9.8 h)	23 h	not assessed

For the body temperature, the paw circumference, the creeping speed, the vertical normalised force obtained with a force plate and the analgesic effect, the maximal estimated effect was expressed as a percentage of control value, a 100% maximum effect indicating a return to control value (no kaolin challenge). Analgesia was assessed by the paw withdrawal time to a heat stimulus and values higher than 100% indicate that there was an analgesic effect of cimicoxib independent of its anti-inflammatory effect i.e. that the paw withdrawal time was longer after the cimicoxib administration than in control condition (no inflammation). For the lameness, the clinical score ranged from 0 (no lameness) to 5 (maximal lameness): a score of 1 corresponding to a slight lameness and a score of 2 to an obvious lameness. The duration of the effect (maximal or total) was directly obtained from raw data. Duration of total effect is the time when the effects of cimicoxib observed are superior to the placebo. Duration of maximal effect is duration during which a steady maximal effect was observed. Values are mean ± SD for the maximal effect and mean and range value for the duration of the maximum effect.

ISSN: 1746-6148