جستجوی مقالات مرتبط با کلیدواژه "pharmacokinetics" در نشریات گروه "دامپزشکی"

Sustained release drug formulations are frequently developed to reduce dosage frequency and to improve outcomes of drug therapy. This study evaluates the pharmacokinetic (PK) parameters of a novel injectable danofloxacin (DANO) formulation in comparison with a conventional product in an animal model. A recently synthesized DANO formulation, prepared by incorporation of DANO-loaded mesoporous silica nanoparticles in liposomes and integration of liposomes in chitosan and β-glycerophosphate solution (lipogel) along with the conventional DANO product were injected subcutaneously (SC) in rabbits. Blood samples were collected at specific time points and DANO concentrations in plasma samples were measured. The PK parameters including maximum concentration (Cmax), time to reach Cmax (Tmax), area under the concentrationversustime curves (AUC), area under the first moment concentration-time curve (AUMC) and mean residence time (MRT) were studied by non-compartmental analyses. The values of MRT (156.00 ± 20.00 hr), AUC (15.30 ± 3.00 µg mL-1 perhr) and Tmax (4.70 ± 1.60 hr) for lipogel formulation were higher than those of the conventional product (8.50 ± 3.60 hr, 3.70 ± 2.00 µg mL-1 per hr and 0.80 ± 0.26 hr, respectively). However, Cmax values for lipogel formulation (0.41 ± 0.15 µg mL-1) were significantly lower than those of the conventional drug product (0.68 ± 0.09 µg mL-1). It was concluded that the novel DANO lipogel effectively slowed down the drug absorption and the incorporation of liposomes in hydrogel could be a useful approach to maintain the therapeutic drug level for a longer period; however, more studies are needed in this field.

Frequent drug dosing and animal handling are usually required in conventional antimicrobial therapy but sustained release formulations can improve compliance.

This study aimed to evaluate the pharmacokinetic (PK) parameters of a novel sustained release enroflox-acin (ENR) hydrogel in comparison to a conventional ENR formulation in rabbit animal model.

A total of 20 rabbits were randomly divided into three groups and received a single dose of ENR or blank by subcutaneous (SC) injection as following: Group 1 (n=8) received ENR (10 mg/kg) using a conventional product (Enrovet®); Group 2 (n=8) received ENR (33.3 mg/kg) using a hydrogel formulation; and Group 3 or control group (n=4) received equal volumes of a blank hydrogel formulation. Blood samples were collected at different time points post-dosing. ENR concen-trations in plasma were estimated by high-performance liquid chromatographic (HPLC) method and PK parameters were calculated using a non-compartmental analysis.

The ENR hydrogel released the drug in a sustained manner with mean residence time (MRT) of 78.4 ± 15.3 h, which was significantly more than that of the conventional formulation (7.39 ± 2.37 h, p <0.05). However, maximal plasma concentration (Cmax) for ENR hydrogel (1.41 ± 0.76 μg/mL) was significantly less than that of the conventional product (2.86 ± 0.79 μg/mL). The relative bioavailability (Frel) was not significantly different between the two formula-tions.

The hydrogel formulation significantly increased the MRT of ENR. Hence, it could be a promising delivery system to prolong the pharmacological activity of ENR in animals and enhance compliance.

The effects of three selective oral inhibitors, fluvoxamine (FLU), ketoconazole (KET), and verapamil (VER), on the pharmacokinetics (PK) of florfenicol (FFC) were investigated in chickens. The chickens were administered orally with saline solution (SAL), FLU (60 mg/kg), KET (25 mg/kg), or VER (9 mg/kg) for 7 consecutive days. Florfenicol was given to the chickens at a single dose of 30 mg/kg orally. Blood samples were collected from each chicken at 0 to 12 h post-administration of FFC. The plasma concentration of FFC was analyzed by high-performance liquid chromatography (HPLC). The AUC of FFC increased and the CLs of FFC decreased with oral co-administration of KET in chickens, and the Cmax of FFC increased with VER. While the AUC, the CLs and the Cmax of FFC were all invariable with FLU. These data suggested that CYP 3A played a key role in the PK of FFC in chickens, however, P-glycoprotein (P-gp) and CYP 1A did not. The results imply that the adverse drug-drug interaction may occur in the use of FFC if the co-administrated drugs are the substrates, inducers or inhibitors of CYP 3A or/and P-gp.

The aim of this study was to evaluate pharmacokinetic profiles of florfenicol after a single dose of intravenous (5.00 mg kg-1 body weight) and oral (40.00 mg kg-1 body weight) administrations in common carp (Cyprinus carpio). The residue depletion of florfenicol was also investigated after oral administration (10.00 mg kg-1 body weight) and bath treatment (5.00 mg L-1) for 10 consecutive days. Pharmacokinetics of florfenicol in plasma after a single dose administration, at 10 time points (0.50, 1, 2, 4, 8, 12, 24, 72, 120 and 168 hr) and florfenicol concentrations in tissues (plasma, liver and muscle) at three time points (1, 7 and 14 days) after 10 consecutive days, were analyzed by high performance liquid chromatography. The peak concentration of florfenicol was 137.02 ng mL-1 and the time to reach peak concentration in plasma was two hr. The elimination half-lives, the volume of distribution at steady state and total body clearance were estimated as 21.40 hr, 0.30 and 0.03 L hr-1, respectively. After drug administration for 10 days, it's concentration in plasma and muscle in oral treatment was significantly more than bath treatment in all days. Drug concentrations in the liver after bath treatment were significantly higher for a shorter period than the concentration in the oral treatment, indicating that higher levels of florfenicol for a longer period can be achieved in the tissues after oral drug administration. According to pharmacokinetic results, florfenicol may be a suitable candidate for the treatment of common bacterial infections in common carp farming.
The aim of this study was to evaluate pharmacokinetic profiles of florfenicol after a single dose of intravenous (5.00 mg kg-1 body weight) and oral (40.00 mg kg-1 body weight) administrations in common carp (Cyprinus carpio). The residue depletion of florfenicol was also investigated after oral administration (10.00 mg kg-1 body weight) and bath treatment (5.00 mg L-1) for 10 consecutive days. Pharmacokinetics of florfenicol in plasma after a single dose administration, at 10 time points (0.50, 1, 2, 4, 8, 12, 24, 72, 120 and 168 hr) and florfenicol concentrations in tissues (plasma, liver and muscle) at three time points (1, 7 and 14 days) after 10 consecutive days, were analyzed by high performance liquid chromatography. The peak concentration of florfenicol was 137.02 ng mL-1 and the time to reach peak concentration in plasma was two hr. The elimination half-lives, the volume of distribution at steady state and total body clearance were estimated as 21.40 hr, 0.30 and 0.03 L hr-1, respectively. After drug administration for 10 days, it's concentration in plasma and muscle in oral treatment was significantly more than bath treatment in all days. Drug concentrations in the liver after bath treatment were significantly higher for a shorter period than the concentration in the oral treatment, indicating that higher levels of florfenicol for a longer period can be achieved in the tissues after oral drug administration. According to pharmacokinetic results, florfenicol may be a suitable candidate for the treatment of common bacterial infections in common carp farming.

Pioglitazone belongs to the thiazolidinedione (TZD) class of antidiabetic agents، with proven efficacy in increasing insulin sensitivity and in the treatment of type 2 diabetes mellitus in humans. Pioglitazone has been proposed as a potential feed additive to reduce insulin resistance and consequently some of the metabolic disorders in transition cows. This study was aimed at determining the pharmacokinetic parameters of pioglitazone following oral administration (PO) or intravenous (IV) injection. Six lactating Holstein cows were randomly assigned into two groups (n=3 cows per group) in a crossover design، and administered with pioglitazone (8 mg/kg BW) either per-oral (PO) or intravenously (IV)، with an 8-day washout period. Blood samples were collected from the jugular vein before and up to 48 h after pioglitazone administration. Plasma pioglitazone concentration was determined by HPLC. The data were analyzed using a non-compartmental model for PO route، and a two-compartmental model for the IV route. The bioavailability of PO-administered pioglitazone was 58% and the highest plasma concentration (Cmax)، the time (tmax) at which the drug reached Cmax، half-life (t1/2)، absorption rate constant (kab) and elimination rate constant (kel) were 11. 57±1. 44 μg/mL، 5. 67±0. 07 h، 7. 10±0. 32 h، 0. 28±0. 09 h-1 and 0. 10±0. 013 h-1، respectively. Elimination half-life (t1/2β)، volume distribution (Vss) and elimination rate constant (kel) after IV injection were 5. 10±0. 62 h، 0. 12±0. 01 L/kg and 0. 47±0. 06 h-1، respectively. Because of the relatively high bioavailability and half-life، pioglitazone may be useful for oral administration as an insulin-sensitizing agent in dairy cows.

The pharmacokinetic parameters of ceftazidime, a third generation cephalosporin, were investigated in six buffalo calves after single intravenous (IV) and intramuscular (IM) administration at a dose rate of 10 mg/kg body weight. Ceftazidime concentrations in plasma and urine were determined by microbiological assay. Ceftazidime disposition was best fitted by a two-compartmental and a one-compartmental open model with first-order elimination after IV and IM dosing, respectively. After IV administration, distribution was rapid (t1/2α = 0.15 ± 0.01 h) with an area under the ceftazidime plasma concentration/time curve (AUC0-∞) of 253.9 ± 7.8 μg/ml.h and a steady state volume of distribution (Vd(ss)) of 0.18 ± 0.01 L.kg-1. The elimination half life (t½β) and total body clearance were 3.4 ± 0.2 h and 39.5 ± 1.2 ml/kg/h, respectively. Following intramuscular administration, the absorption half life (t1/2ka), peak plasma concentration (Cmax), time to peak plasma concentration (Tmax), AUC0-∞ and bioavailability were 0.25 ± 0.04 h, 45.8 ± 2.7 μg/ml, 0.75 h, 207.9 ± 9.9 μg/ml.h and 81.7 ± 5.9%, respectively. Urinary excretion of ceftazidime was less than 55% 36 h post administration. In vitro plasma protein binding of ceftazidime was 13.1 ± 1.1%. To maintain minimum therapeutic concentration of 4 μg/ml, a satisfactory dosage regimen of ceftazidime in buffalo calves would be 9.4 mg/kg to be repeated at 12 h intervals. In conclusion, ceftazidime (10 mg/kg, IM) shows favorable pharmacokinetic behavior in buffalo calves.