Skin permeability and pharmacokinetics of diclofenac epolamine administered by dermal patch in Yorkshire-Landrace pigs

Figures & data

Figure 1 Schematic for the placement of the dermal patch (divided into six pieces) and sampling for animals in group 1 (dermal treatment group) (A) and group 2 (oral treatment group) (B).

Note: Samples were collected randomly from the six identified sites.

Table 1 Analytical performance of the UPLC/MS-MS methods used for the analyses of diclofenac in tissue homogenates and plasma samples from Yorkshire-Landrace pigs

	Skin homogenate (low level)			Muscle homogenate (low level)
	Low QC	Mid QC	High QC	Low QC	Mid QC	High QC
QC concentration (ng/mL)	0.0225	0.570	5.70	0.00225	0.0225	0.570
Average % bias	−4.9	−6.8	−8.4	−0.9	9.3	−2.1
% CV	4.0	3.8	2.0	6.6	8.0	3.4
n	4	4	4	4	4	4
	Skin homogenate (high level)			Muscle homogenate (high level)
	Low QC	Mid QC	High QC	Low QC	Mid QC	High QC
QC concentration (ng/mL)	6.0	60.0	1500	3.0	30.0	750
Average % bias	−4.0	−1.8	−4.0	1.3	3.7	2.3
% CV	4.2	1.3	1.7	6.4	8.0	4.4
n	8	8	8	8	8	8
	Plasma
	Low QC	Mid QC	High QC	Dilution QC 1	Dilution QC 2	Dilution QC 3
QC concentration (ng/mL)	0.003	0.050	0.750	10.0	10.0	1000
Average % bias	−2.3	1.4	−5.5	−8.8	−5.4	6.0
% CV	6.9	4.0	6.0	2.8	2.5	4.5
n	16	16	16	4	4	4

Abbreviations: UPLC/MS-MS, ultra performance liquid chromatography tandem mass spectrometric; QC, quality control; CV, coefficient of variation.

Table 2 PK parameters of diclofenac in female Yorkshire-Landrace pigs following oral administration or dermal patch application

Route	Matrix (side)	Cmax (ng/mL or ng/g)			Tmax (h)			AUC(0–11.5 h) (ng · h/mL or ng · h/g)
		Mean	SD	n	Mean	SD	n	Mean	SD	n
Oral	Plasma	9640	906	6	2	0	6	46,000	4817	6
	Muscle	1160	256	6	2	0	6	5867	1455	6
	Skin	1500	319	6	3.3	1.4	6	9600	1817	6
Dermal	Plasma	3.49	5.57	6	5.3	5	6	25.2	39.0	6
	Muscle (treated)	879	632	6	6.7	4.2	6	4117	2633	6
	Muscle (untreated)	0.652	0.926	6	4.2	3.2	6	5.0	6.7	6
	Skin (treated)	19,200	2350	6	5.2	3	6	161,167	24,333	6
	Skin (untreated)	2.4	2.51	6	4.2	3.2	6	14.3	15.6	6

Notes: Treated: dermal patch applied to the right-dorsal lumbar region; untreated: samples obtained but no patch was administered.

Abbreviations: PK, pharmacokinetic; C_max, highest drug concentration observed in plasma/tissues; T_max, time at which C_max was first observed; AUC_{(0–11.5 h)}, area under the plasma/tissue drug concentration-time curve for 0–11.5 hours.

Figure 2 Diclofenac concentrations in the plasma (A), muscle (B), and skin (C) of female Yorkshire-Landrace pigs following oral administration or dermal patch application.

Figure 3 Muscle to skin concentration ratios of diclofenac after the application of dermal patch in Yorkshire-Landrace pigs.