Pharmacokinetics of chloramphenicol in sheep after intravenous, intramuscular and subcutaneous administration

The pharmacokinetics of chloramphenicol were studied in sheep after 3 single intravenous (IV), intramuscular (IM) and subcutaneous (SC) administrations (30 mg/kg). The two extravascular routes were studied during a crossover trial for a bioequivalence test. After IV and SC administrations, the plasma-concentration time graphs were characteristic of a two-compartment model, and after IM administration it was characteristic of a monocompartment model. The two routes of absorption were not bioequivalent. Using the kinetic values, multidose regimens to maintain the therapeutic chloramphenicol blood level (5 micrograms/ml) were proposed: 60 mg/kg every 12 hours for 72 hours for the IM administration and 45 mg/kg administered subcutaneously according to the same regimen. A study of the chloramphenicol residues in tissues was carried out. Chloramphenicol residues remained at the injection site, and 400 hours would be necessary to obtain the level of 10 micrograms/kg. Determination of the creatinine phosphokinase serum values showed that the subcutaneous route induced less damage to muscle than the intramuscular route.     

Pharmacokinetics after intravenous, intramuscular and subcutaneous administration of difloxacin in sheep

The disposition kinetics of difloxacin, a fluoroquinolone antibiotic, after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration were determined in sheep at a single dose of 5mg/kg. The concentration-time data were analysed by compartmental (after IV dose) and non-compartmental pharmacokinetics method (after IV, IM and SC administration). Plasma concentrations of difloxacin were determined by high performance liquid chromatography with fluorescence detection. Steady-state volume of distribution (V(ss)) and clearance (Cl) of difloxacin after IV administration were 1.68+/-0.21L/kg and 0.21+/-0.03L/hkg, respectively. Following IM and SC administration difloxacin achieved maximum plasma concentration of 1.89+/-0.55 and 1.39+/-0.14mg/L at 2.42+/-1.28 and 5.33+/-1.03h, respectively. The absolute bioavailabilities after IM and SC routes were 99.92+/-26.50 and 82.35+/-25.65%, respectively. Based on these kinetic parameters, difloxacin is likely to be effective in sheep.     

Pharmacokinetics after intravenous, intramuscular and subcutaneous administration of moxifloxacin in sheep

The disposition kinetics of moxifloxacin, a fluoroquinolone antibiotic, after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration was determined in sheep at a single dose of 5 mg/kg. The concentration-time data were analysed by compartmental (after IV dose) and non-compartmental (after IV, IM and SC administration) pharmacokinetic methods. Plasma concentrations of moxifloxacin were determined by high performance liquid chromatography with fluorescence detection. Steady-state volume of distribution (V_ss) and clearance (Cl) of moxifloxacin after IV administration were 2.03 ± 0.36 L/kg and 0.39 ± 0.04 L/h kg, respectively. Following IM and SC administration, moxifloxacin achieved maximum plasma concentration of 1.66 ± 0.62 mg/L and 0.90 ± 0.19 mg/L at 2.25 ± 0.88 h and 3.25 ± 1.17 h, respectively. The absolute bioavailabilities after IM and SC routes were 96.12 ± 32.70% and 102.20 ± 23.76%, respectively. From these data (kinetic parameters and absence of adverse reactions) moxifloxacin may be a potentially useful antibiotic in sheep.     

Pharmacokinetics of norfloxacin after intravenous,intramuscular and subcutaneous administration to rabbits

The disposition kinetics of norfloxacin, after intravenous, intramuscular and subcutaneous administration was determined in rabbits at a single dose of 10 mg/kg. Six New Zealand white rabbits of both sexes were treated with aqueous solution of norfloxacin (2%). A cross‐over design was used in three phases (2 × 2 × 2), with two washout periods of 15 days. Plasma samples were collected up to 72 hr after treatment, snap‐frozen at ?45°C and analysed for norfloxacin concentrations using high‐performance liquid chromatography. The terminal half‐life for i.v., i.m. and s.c. routes was 3.18, 4.90 and 4.16 hr, respectively. Clearance value after i.v. dosing was 0.80 L/h·kg. After i.m. administration, the absolute bioavailability was (mean ± SD ) 108.25 ± 12.98% and the C_max was 3.68 mg/L. After s.c. administration, the absolute bioavailability was (mean ± SD ) 84.08 ± 10.36% and the C_max was 4.28 mg/L. As general adverse reactions were not observed in any rabbit and favourable pharmacokinetics were found, norfloxacin at 10 mg/kg after i.m. and s.c. dose could be effective in rabbits against micro‐organisms with MIC ≤0.14 or 0.11 μg/mL , respectively.     

Pharmacokinetics of spiramycin after intravenous, intramuscular and subcutaneous administration in lactating cows

Spiramycin is a macrolide antibiotic that is active against most of the microorganisms isolated from the milk of mastitic cows. This work investigated the disposition of spiramycin in plasma and milk after intravenous, intramuscular and subcutaneous administration. Twelve healthy cows were given a single injection of spiramycin at a dose of 30,000 IU/kg by each route. Plasma and milk were collected post injection. Spiramycin concentration in the plasma was determined by a high performance liquid chromatography method, and in the milk by a microbiological method. The mean residence time after intravenous administration was significantly longer (P less than 0.01) in the milk (20.7 +/- 2.7 h) than in plasma (4.0 +/- 1.6 h). An average milk-to-plasma ratio of 36.5 +/- 15 was calculated from the area concentration-time curves. Several pharmacokinetic parameters were examined to determine the bioequivalence of the two extravascular routes. The dose fraction adsorbed after intramuscular or subcutaneous administration was almost 100% and was bioequivalent for the extravascular routes, but the rates of absorption, the maximal concentrations and the time to obtain them differed significantly between the two routes. Spiramycin quantities excreted in milk did not differ between the two extravascular routes but the latter were not bioequivalent for maximal concentration in the milk. However, the two routes were bio-equivalent for the duration of time the milk concentration exceeded the minimal inhibitory concentration (MIC) of various pathogens causing infections in the mammary gland.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of gamithromycin after intravenous and subcutaneous administration in pigs

The aim of this study was to investigate the pharmacokinetic properties of gamithromycin in pigs after an intravenous (i.v.) or subcutaneous (s.c.) bolus injection of 6 mg/kg body weight. The plasma concentrations of gamithromycin were determined using a validated high-performance liquid chromatography–tandem mass spectrometry method, and the pharmacokinetics were noncompartmentally analysed.     

Pharmacokinetics of cefuroxime after intravenous,intramuscular, and subcutaneous administration to dogs

Cefuroxime pharmacokinetic profile was investigated in 6 Beagle dogs after single intravenous, intramuscular, and subcutaneous administration at a dosage of 20 mg/kg. Blood samples were withdrawn at predetermined times over a 12‐h period. Cefuroxime plasma concentrations were determined by HPLC. Data were analyzed by compartmental analysis. Peak plasma concentration (C_max), time‐to‐peak plasma concentration (T_max), and bioavailability for the intramuscular and subcutaneous administration were (mean ± SD) 22.99 ± 7.87 μg/mL, 0.43 ± 0.20 h, and 79.70 ± 14.43% and 15.37 ± 3.07 μg/mL, 0.99 ± 0.10 h, and 77.22 ± 21.41%, respectively. Elimination half‐lives and mean residence time for the intravenous, intramuscular, and subcutaneous administration were 1.12 ± 0.19 h and 1.49 ± 0.21 h; 1.13 ± 0.13 and 1.79 ± 0.24 h; and 1.04 ± 0.23 h and 2.21 ± 0.23 h, respectively. Significant differences were found between routes for K_a, MAT, C_max, T_max, t_½(a), and MRT. T > MIC = 50%, considering a MIC of 1 μg/mL, was 11 h for intravenous and intramuscular administration and 12 h for the subcutaneous route. When a MIC of 4 μg/mL is considered, T > MIC = 50% for intramuscular and subcutaneous administration was estimated in 8 h.     

Pharmacokinetics of diclofenac in sheep following intravenous and intramuscular administration

OBJECTIVES: The aim of this work was to examine the pharmacokinetics of diclofenac (DCLF) in sheep after intravenous (IV) and intramuscular (IM) dosing. ANIMALS: Healthy male Najdi sheep. MATERIALS AND METHODS: Diclofenac (1 mg kg(-1)) was administered to ten clinically healthy-male Najdi sheep IV or IM (n = 5 each). Blood samples (5 mL) were collected and serum was separated for drug analysis by high-performance liquid chromatography with UV detection. Diclofenac pharmacokinetic parameters were determined by noncompartmental analysis. RESULTS: Diclofenac is quickly eliminated from sheep with a terminal T(1/2lambda) of 2-3 hours for both routes of administration. Total DCLF clearance after IV and IM administration was 87.86 +/- 24.10 and 85.69 +/- 40.76 mL kg(-1) hour(-1) respectively. The absolute bioavailability of IM DCLF appears to be approximately 100%. CONCLUSIONS AND CLINICAL RELEVANCE: The drug should be administered two to three times daily in sheep by IM or IV injection to maintain therapeutic concentrations. Additional studies are needed to evaluate the route of elimination of DCLF in sheep including metabolites formation and the significance of enterohepatic circulation.     

Pharmacokinetics of ceftriaxone after intravenous, intramuscular and subcutaneous administration to domestic cats

The pharmacokinetic properties of ceftriaxone, a third-generation cephalosporin, were investigated in five cats after single intravenous, intramuscular and subcutaneous administration at a dosage of 25 mg/kg. Ceftriaxone MICs for some gram-negative and positive strains isolated from clinical cases were determined. Efficacy predictor (t > MIC) was calculated. Serum ceftriaxone disposition was best fitted by a bicompartmental and a monocompartmental open models with first-order elimination after intravenous and intramuscular and subcutaneous dosing, respectively. After intravenous administration, distribution was fast (t1/2d 0.14 +/- 0.02 h) and moderate as reflected by the volume of distribution (V(d(ss))) of 0.57 +/- 0.22 L/kg. Furthermore, elimination was rapid with a plasma clearance of 0.37 +/- 0.13 L/h.kg and a t1/2 of 1.73 +/- 0.23 h. Peak serum concentration (Cmax), tmax and bioavailability for the intramuscular administration were 54.40 +/- 12.92 microg/mL, 0.33 +/- 0.07 h and 85.72 +/- 14.74%, respectively; and for the subcutaneous route the same parameters were 42.35 +/- 17.62 microg/mL, 1.27 +/- 0.95 h and 118.28 +/- 39.17%. Ceftriaxone MIC for gram-negative bacteria ranged from 0.0039 to >8 microg/mL and for gram-positive bacteria from 0.5 to 4 microg/mL. t > MIC was in the range 83.31-91.66% (10-12 h) of the recommended dosing interval (12 h) for Escherichia coli (MIC90 = 0.2 microg/mL).     

Pharmacokinetics of enrofloxacin following intravenous and intramuscular administration in Angora rabbits

The pharmacokinetic behaviour and bioavailability of enrofloxacin (ENR) were determined after single intravenous (iv) and intramuscular (im) administrations of 5mg/kg bw to six healthy adult Angora rabbits. Plasma ENR concentrations were measured by high performance liquid chromatography. The pharmacokinetic data were best described by a two-compartment open model. ENR pharmacokinetic parameters were similar (p>0.05) for iv and im administrations in terms of AUC0-infinity, t1/2beta and MRT. ENR was rapidly (t1/2a, 0.05 h) and almost completely (F, 87%) absorbed after im injection. In conclusion, the pharmacokinetic properties of ENR following iv and im administration in Angora rabbits are similar to other rabbit breeds, and once or twice daily iv and im administrations of ENR at the dose of 5mg/kg bw, depending upon the causative pathogen and/or severity of disorders, may be useful in treatment of infectious diseases caused by sensitive pathogens in Angora rabbits.     

Pharmacokinetics of amikacin in the horse following intravenous and intramuscular administration

The pharmacokinetics of amikacin sulfate (AK) were studied in the horse after intravenous (i.v.) and intramuscular (i.m.) administration. Serum (Cs), synovial (Csf) and peritoneal (Cpf) fluid concentrations of the drug were measured. Doses of 4.4, 6.6 and 11.0 mg/kg were given. The concentrations at 15 min following i.v. injection were 30.3 +/- 0.3, 61.2 +/- 6.9 and 122.8 +/- 7.4 micrograms/ml, respectively, for the 4.4, 6.6 and 11.0 mg/kg doses. Mean peak Cs values after the intramuscular injections occurred at 1.0 h post-injection and were 13.3 +/- 1.6, 23.0 +/- 0.6 and 29.8 +/- 3.2 micrograms/ml, respectively. The t 1/2 of amikacin was 1.44, 1.57 and 1.14 h for the 4.4, 6.6 and 11.0 mg/kg doses, respectively. In this study, minimum inhibitory concentrations (MIC) of amikacin sulfate were determined for six pathogens. Based on the MIC and the pharmacokinetic parameters, it would appear that the usual therapeutic dose of amikacin would be between 4.4 and 6.6 mg/kg twice daily and, for the more serious life-threatening infections, dosing three times a day.     

Pharmacokinetics of cefonicid in lactating goats after intravenous,intramuscular and subcutaneous administration,and after a long-acting formulation for subcutaneous administration

The single-dose disposition kinetics of cefonicid were determined in clinically normal lactating goats (n = 6) after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration of a conventional formulation, and after subcutaneous administration of a long-acting formulation (SC-LA). Cefonicid concentrations were determined by high performance liquid chromatography with ultraviolet detection. The concentration–time data were analysed by noncompartmental pharmacokinetic methods. Steady-state volume of distribution (V_ss) and clearance (Cl) of cefonicid after IV administration were 0.14 ± 0.03 L/kg and 0.51 ± 0.07 L/h·kg, respectively. Following IM, SC and SC-LA administration, cefonicid achieved maximum plasma concentrations of 14.46 ± 0.82, 11.98 ± 1.92 and 17.17 ± 2.45 mg/L at 0.26 ± 0.13, 0.42 ± 0.13 and 0.83 ± 0.20 hr, respectively. The absolute bioavailabilities after IM, SC and SC-LA routes were 75.34 ± 11.28%, 71.03 ± 19.14% and 102.84 ± 15.155%, respectively. After cefonicid analysis from milk samples, no concentrations were found above LOQ at any sampling time. From these data, cefonicid administered at 20 mg/kg each 12 hr after SC-LA could be effective to treat bacterial infections in lactating animals not affected by mastitis problems.     

Pharmacokinetics of tilmicosin in beef cattle following intravenous and subcutaneous administration

The intravenous pharmacokinetic profile of tilmicosin is yet to be achieved because of the cardiovascular effects of tilmicosin. This study summarizes two pharmacokinetic studies that provided complete pharmacokinetic profile of tilmicosin in cattle. The first study was a pharmacokinetic study of tilmicosin in beef calves dosed by i.v. infusion over 5 h. The second study was a subcutaneous (s.c.) pharmacokinetic study comparing the pharmacokinetic profile of tilmicosin in light (approximately 170 kg) and heavy (approximately 335 kg) beef cattle and comparing the labeled dose range of 10 or 20 mg/kg dose. The data from the two different studies were used to calculate bioavailability values, which support the assumption that tilmicosin is 100% bioavailable in cattle. The results from the second study showed that the weight of an animal when administered tilmicosin does not have a significant effect on exposure, but did demonstrate that doubling the dose of tilmicosin administered doubles the systemic exposure to tilmicosin.     

Pharmacokinetics of sodium baicalin following intravenous and intramuscular administration to piglets

The purpose of this study was to determine the pharmacokinetics of baicalin after intravenous and intramuscular administration of sodium baicalin at 50 mg/kg to piglets. Plasma baicalin levels were determined by high‐performance liquid chromatography. The plasma concentration–time data of baicalin for both administration routes were best described by two‐compartmental open model. The area under the plasma concentration–time curve and the elimination half‐lives were 77.47 ± 6.14 µg/ml × h and 1.73 ± 0.16 hr for intravenous and 64.85 ± 5.67 µg/ml × h and 2.42 ± 0.15 hr for intramuscular administration, respectively. The apparent volume of distribution and body clearance were 1.63 ± 0.23 L/kg and 2.74 ± 0.30 L h^?1 kg^?1 for intravenous and 0.51 ± 0.10 L/kg and 0.78 ± 0.08 L h^?1 kg^?1 for intramuscular routes, respectively. An intramuscular injection of sodium baicalin in piglets resulted in rapid and complete absorption, with a mean maximal plasma concentration of 77.28 ± 7.40 µg/ml at 0.17 hr and a high absolute bioavailability of 83.73 ± 5.53%.     

Pharmacokinetics of benzydamine in dairy cows following intravenous or intramuscular administration

Five lactating cows were given benzydamine hydrochloride by rapid intravenous (0.45 mg/kg) and by intramuscular (0.45 and 1.2 mg/kg) injection in a crossover design. The bioavailability, pharmacokinetic parameters and excretion in milk of benzydamine were evaluated. After intravenous administration, the disposition kinetics of benzydamine was best described using a two-compartment open model. Drug disposition and elimination were fast (t _1/2: 11.13±3.76 min;t _1/2: 71.98±24.75 min; MRT 70.69±11.97 min). Benzydamine was widely distributed in the body fluids and tissues (V _d(area): 3.549±1.301 L/kg) and characterized by a high value for body clearance (33.00±5.54 ml/kg per min). After intramuscular administration the serum concentration-time curves fitted a one-compartment open model. Following a dose of 0.45 mg/kg, theC _max value was 38.13±4.2 ng/ml at at _max of 67.13±4.00 min; MAT and MRT were 207.33±22.64 min and 278.01±12.22 min, respectively. Benzydamine bioavailability was very high (92.07%±7.08%). An increased intramuscular dose (1.2 mg/kg) resulted in longer serum persistence (MRT 420.34±86.39 min) of the drug, which was also detectable in milk samples collected from both the first and second milking after treatment.Abbreviations HPLC high-pressure liquid chromatography - IC50 concentration to inhibit the activity of an organism by 50% - IM intramuscular(ly) - IV intravenous(ly) - NSAID non-steroidal antiinflammatory drugs - pK _a negative logarithm of the ionization constant (K _a) of a drug; other abbreviations are listed in footnotes to tables