The dose regimen formulation of doxycycline hydrochloride and florfenicol injection based on ex vivo pharmacokinetic-pharmacodynamic modeling against the Actinobacillus pleuropneumoniae in pigs

Table 1 The PK parameters after administration (20 mg/kg, IM) in plasma (mean ± SD, n = 6)

Parameters	Unit	Single FF	FF of compound		Single DoxHcl	DoxHcl of compound
Parameters	Unit	Healthy	Healthy	Diseased	Healthy	Healthy	Diseased
K₁₂	h	0.08 ± 0.04	0.08 ± 0.03	0.06 ± 0.03	0.08 ± 0.01	0.02 ± 0.01	0.03 ± 0.01
K₂₁	h	0.09 ± 0.02	0.14 ± 0.04	0.11 ± 0.01	0.16 ± 0.02	0.14 ± 0.03	0.14 ± 0.01
AUC_0-24h	h·μg/mL	91.86 ± 4.52	105.52 ± 1.46	115.05 ± 1.88	68.20 ± 3.98	72.77 ± 1.41	73.29 ± 1.05
T_max	h	3.41 ± 0.27	3.45 ± 0.21	3.67 ± 0.08	1.86 ± 0.14	1.97 ± 0.06	2.04 ± 0.07
C_max	μg/mL	4.13 ± 0.11	4.08 ± 0.09	4.09 ± 0.05	3.63 ± 0.14	3.58 ± 0.07	3.60 ± 0.09
T_1/2α	h	3.62 ± 1.21	3.04 ± 0.96	4.12 ± 1.49	4.65 ± 2.73	4.20 ± 0.75	3.76 ± 0.59
T_1/2β	h	22.61 ± 2.15	20.57 ± 1.66	22.85 ± 1.76	16.32 ± 1.38	14.90 ± 0.54	15.37 ± 0.82
CL/F	L/kg/h	0.22 ± 0.01	0.19 ± 0.003	0.17 ± 0.003	0.29 ± 0.02	0.27 ± 0.005	0.27 ± 0.004
V₁/F	L/kg	3.03 ± 0.60	3.29 ± 0.42	3.45 ± 0.55	4.50 ± 0.69	4.81 ± 0.18	4.69 ± 0.28
V₂/F	L/kg	2.58 ± 0.74	1.75 ± 0.49	1.65 ± 0.79	1.44 ± 0.65	0.72 ± 0.20	0.94 ± 0.40

The data were substituted into the first-order absorption two-compartment model in WinNonlin software to fit. K₁₂ first-order rate constant of drug transport from the central compartment to the peripheral compartment, K₂₁ first-order rate constant of drug transport from the peripheral chamber to the central chamber, AUC_0-24h the area under the concentration-time curve, C_max maximal drug concentration, T_max time to reach, C_max, T_1/2α the distribution half-life, T_1/2β the elimination half-life, CL/F total body clearance as a function of bioavailability, V₁/F distribution volume of the central chamber as a function of bioavailability, V₂/F distribution volume of the peripheral chamber as a function of bioavailability