Pharmacokinetics of ciprofloxacin in carp,African catfish and rainbow trout

Summary

The plasma disposition of ciprofloxacin was studied in carp, African catfish and trout after intravenous (IV) and intramuscular (IM) administration at a dose rate of 15 mg/ kg. Pharmacokinetic analysis of IV data showed that ciprofloxacin was well distributed (distribution volume V area): 3.08 ‐ 5.59 litre/kg) and exhibited a similar elimination half‐life of about 14 h in these 3 fish species. After IM administration to carp and trout a rapid absorption was noticed; the maximum ciprofloxacin plasma concentrations (mean: 3.49 and 2.37 pg/ml, respectively), were achieved within I h after injection. At the dose level applied, ciprofloxacin has potential therapeutic value for 2–5 days especially against gram‐negative bacterial fish pathogens.     

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 enrofloxacin after intravenous and intramuscular administration in Angora goats.

Pharmacokinetics and bioavailability of enrofloxacin were determined after single intravenous (IV) and intramuscular (IM) administrations of 5 mg/kg body weight (BW) to 5 healthy adult Angora goats. Plasma enrofloxacin concentrations were measured by high performance liquid chromatography. Pharmacokinetics were best described by a 2-compartment open model. The elimination half-life and volume of distribution after IV and IM administrations were similar (t1/2beta, 4.0 to 4.7 h and Vd(ss),1.2 to 1.5 L/kg, respectively). Enrofloxacin was rapidly (t1/2a, 0.25 h) and almost completely absorbed (F, 90%) after IM administration. Mean plasma concentrations of enrofloxacin at 24 h after IV and IM administration (0.07 and 0.09 microg/mL, respectively) were higher than the minimal inhibitory concentration (MIC) values for most pathogens. In conclusion, once-daily IV and IM administration of enrofloxacin (5 mg/kg BW) in Angora goats may be useful in treatment of infectious diseases caused by sensitive pathogens.     

Disposition kinetics of enrofloxacin (Baytril 5%) in sheep and goats following intravenous and intramuscular injection using a microbiological assay

The pharmacokinetics of enrofloxacin were determined in Desert sheep and Nubian goats after intravenous and intramuscular administration of Baytril at the dose of 5mgkg(-1) bodyweight. A two compartment open model best represented the intravenous plasma concentration versus time data in both species. Comparisons between the means of the pharmacokinetic parameters obtained after intravenous administration of enrofloxacin (Baytril) revealed a significantly smaller distribution rate constant (lambda(1)) and consequently a shorter half-life time of distribution in sheep (P<0.05). A larger volume of the central compartment (Vc) was observed in goats (P<0.05). Similar values were obtained for sheep and goats for the remaining parameters.Plasma concentrations versus time data of enrofloxacin after 5mgkg(-1) intramuscular administration of Baytril in sheep and goats were adequately described by one-compartment open model with first order absorption and elimination. There were no significant differences between sheep and goats in any of the estimated pharmacokinetic parameters.The results indicate that the pharmacokinetics of enrofloxacin did not differ significantly between sheep and goats; similar intravenous and intramuscular dose rates of enrofloxacin should therefore be applicable to both species. Owing to the high variations in MIC (minimal inhibitory concentration) of sensitive veterinary pathogens, it is recommended that enrofloxacin dosage regimens be calculated according to the sensitivity of the individual pathogen, site of infection and clinical response, than by following a preset dosage regimen.     

Pharmacokinetic profiles of metamizole (dipyrone) active metabolites in goats and its residues in milk

Metamizole (dipyrone, MET) is a nonopioid analgesic drug commonly used in human and veterinary medicine. The aim of this study was to assess two major active metabolites of MET, 4‐methylaminoantipyrin (MAA) and 4‐aminoantipyrin (AA), in goat plasma after intravenous (IV) and intramuscular (IM) administration. In addition, metabolite concentration in milk was monitored after IM injection. Six healthy female goats received MET at a dose of 25 mg/kg by IV and IM routes in a crossover design study. The blood and milk samples were analyzed using HPLC coupled with ultraviolet detector and the plasma vs concentration curves analyzed by a noncompartmental model. In the goat, the MET rapidly converted into MAA and the mean maximum concentration was 183.97 μg/ml (at 0.08 hr) and 51.94 μg/ml (at 0.70 hr) after IV and IM administration, respectively. The area under the curve and mean residual time values were higher in the IM than the IV administered goats. The average concentration of AA was lower than MAA in both groups. Over 1 μg/ml of MAA was found in the milk (at 48 hr) after MET IM administration. In conclusion, IM is considered to be a better administration route in terms of its complete absorption with long persistence in the plasma. However, this therapeutic option should be considered in light of the likelihood of there being milk residue.     

Pharmacokinetics of intravenously and intramuscularly administered ticarcillin and clavulanic acid in foals

Serum concentrations of ticarcillin and clavulanic acid were measured in healthy foals (2 to 6 months old) given the drugs in combination by intravenous and intramuscular routes of administration. Five foals were administered 50 mg of ticarcillin/kg of body weight and 1.67 mg of clavulanic acid/kg, IV. Five foals were administered 100 mg of ticarcillin/kg and 3.33 mg of clavulanic acid/kg, IV, and 4 of those 5 were given the same combined dose IM. The elimination half-life of ticarcillin for intravenous administration was 0.83 hour for the low dosage and 0.96 hour for the high dosage. After intramuscular administration, the half-life of elimination was 2.9 hours, with bioavailability of 54.6%. For IV administered clavulanic acid, the elimination half-life was 0.65 hour for the low dosage and 0.74 hour for the high dosage. After intramuscular administration, the elimination half-life was 0.92 hour, and bioavailability was 68.1%. A combined dosage, 50 mg of ticarcillin/kg and 1.67 mg of clavulanic acid/kg, given every 6 hours is recommended.     

Pharmacokinetics of levosulpiride after single‐dose administration in goats (Capra hircus) by different routes of administration

Levosulpiride (LSP) is the l‐enantiomer of sulpiride, and LSP recently replacing sulpiride in several EU countries. Several studies about LSP in humans are present in the literature, but neither pharmacodynamic nor pharmacokinetic data of LSP is present for veterinary species. The aim of this study was to assess the pharmacokinetic profile of LSP after intravenous (IV), intramuscular (IM), and oral (PO) administration in goats. Animals (n = 6) were treated with 50 mg LSP by IV, IM, and PO routes according to a randomized cross‐over design (3 × 3 Latin‐square). Blood samples were collected prior and up to 24 hr after LSP administration and quantified using a validated HPLC method with fluorescence detection. IV and IM administration gave similar concentration versus time curve profiles. The IM mean bioavailability was 66.97%. After PO administration, the drug plasma concentrations were detectable only in the time range 1.5–4 hr, and the bioavailability (4.73%) was low. When the AUC was related to the administered dose in mg/kg, there was a good correlation in the IV and IM groups, but very low correlation for the PO route. In conclusion, the IM and IV administrations result in very similar plasma concentrations. Oral dosing of LSP in goats is probably not viable as its oral bioavailability was very low.     

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 of tobramycin in ducks and sex-related differences

The aims of the present study were to determine the disposition of tobramycin after single intravenous (IV) and intramuscular (IM) injections in ducks, and to establish any sex-related differences. Tobramycin sulfate was administered as a 2.5% water solution in a cross-over design at a dose of 5 mg/kg to 12 healthy ducks (six males and six females). Concentrations of the drug in serum were determined by a microbiological assay. The serum pharmacokinetic values for tobramycin were best represented using a one- or two-compartment open model, depending on the method of administration. Non-compartment analysis was also performed after IV administration. Tobramycin had a low degree of distribution and a relatively fast elimination. The mean volume of distribution in ducks (males and females) was higher than that reported in pigeons but lower than in chickens, with a slower rate of elimination. The IM injection resulted in a fast and complete absorption. The rate of elimination after IM administration was about twice as slow as in other avian species. Sex-related variations in tobramycin pharmacokinetics were similar to those reported for kanamycin and apramycin in hens and roosters.     

Pharmacokinetics of enrofloxacin after oral,intramuscular and bath administration in crucian carp (Carassius auratus gibelio)

The pharmacokinetics of enrofloxacin (ENR) was studied in crucian carp (Carassius auratus gibelio) after single administration by intramuscular (IM) injection and oral gavage (PO) at a dose of 10 mg/kg body weight and by 5 mg/L bath for 5 hr at 25°C. The plasma concentrations of ENR and ciprofloxacin (CIP) were determined by HPLC. Pharmacokinetic parameters were calculated based on mean ENR or CIP concentrations using WinNonlin 6.1 software. After IM, PO and bath administration, the maximum plasma concentration (C_max) of 2.29, 3.24 and 0.36 μg/ml was obtained at 4.08, 0.68 and 0 hr, respectively; the elimination half‐life (T_1/2β) was 80.95, 62.17 and 61.15 hr, respectively; the area under the concentration–time curve (AUC) values were 223.46, 162.72 and 14.91 μg hr/ml, respectively. CIP, an active metabolite of enrofloxacin, was detected and measured after all methods of drug administration except bath. It is possible and practical to obtain therapeutic blood concentrations of enrofloxacin in the crucian carp using IM, PO and bath immersion administration.     

The pharmacokinetics, metabolism and urinary detection time of tramadol in camels

The pharmacokinetics of tramadol in camels (Camelus dromedarius) were studied following a single intravenous (IV) and a single intramuscular (IM) dose of 2.33 mg kg(-1) bodyweight. The drug's metabolism and urinary detection time were also investigated. Following both IV and IM administration, tramadol was extracted from plasma using an automated solid phase extraction method and the concentration measured by gas chromatography-mass spectrometry (GC/MS). The plasma drug concentrations after IV administration were best fitted by an open two-compartment model. However a three-compartment open model best fitted the IM data. The results (means+/-SEM) were as follows: after IV drug administration, the distribution half-life (t(1/2)(alpha)) was 0.22+/-0.05 h, the elimination half-life (t(1/2)(beta)) 1.33+/-0.18 h, the total body clearance (Cl(T)) 1.94+/-0.18 L h kg(-1), the volume of distribution at steady state (Vd(ss)) 2.58+/-0.44 L kg(-1), and the area under the concentration vs. time curve (AUC(0-infinity)) 1.25+/-0.13 mg h L(-1). Following IM administration, the maximal plasma tramadol concentration (C(max)) reached was 0.44+/-0.07 microg mL(-1) at time (T(max)) 0.57+/-0.11h; the absorption half-life (t(1/2 ka)) was 0.17+/-0.03 h, the (t(1/2)(beta)) was 3.24+/-0.55 h, the (AUC(0-infinity)) was 1.27+/-0.12 mg h L(-1), the (Vd(area)) was 8.94+/-1.41 L kg(-1), and the mean systemic bioavailability (F) was 101.62%. Three main tramadol metabolites were detected in urine. These were O-desmethyltramadol, N,O-desmethyltramadol and/or N-bis-desmethyltramadol, and hydroxy-tramadol. O-Desmethyltramadol was found to be the main metabolite. The urinary detection times for tramadol and O-desmethyltramadol were 24 and 48 h, respectively. The pharmacokinetics of tramadol in camels was characterised by a fast clearance, large volume of distribution and brief half-life, which resulted in a short detection time. O-Desmethyltramadol detection in positive cases would increase the reliability of reporting tramadol abuse.     

Pharmacokinetics and selected behavioral responses to butorphanol and its metabolites in goats following intravenous and intramuscular administration

Objective To evaluate disposition of a single dose of butorphanol in goats after intravenous (IV) and intramuscular (IM) administration and to relate behavioral changes after butorphanol administration with plasma concentrations. Design Randomized experimental study. Animals Six healthy 3‐year‐old neutered goats (one male and five female) weighing 46.5 ± 10.5 kg (mean ± D). Methods Goats were given IV and IM butorphanol (0.1 mg kg^?1) using a randomized cross‐over design with a 1‐week interval between treatments. Heparinized blood samples were collected at fixed intervals for subsequent determination of plasma butorphanol concentrations using an enzyme linked immunosorbent assay (ELISA). Pharmacokinetic values (volume of distribution at steady state [Vd_SS], systemic clearance [Cl_TB], extrapolated peak plasma concentration [C₀] or estimated peak plasma concentration [C_MAX], time to estimated peak plasma concentration [T_MAX], distribution and elimination half‐lives [t_1/2], and bioavailability) were calculated. Behavior was subjectively scored. A two‐tailed paired t‐test was used to compare the elimination half‐lives after IV and IM administration. Behavioral scores are reported as median (range). A Friedman Rank Sums test adjusted for ties was used to analyze the behavioral scores. A logit model was used to determine the effect of time and concentration on behavior. A value of p < 0.05 was considered significant. Results Volume of distribution at steady state after IV administration of butorphanol was 1.27 ± 0.73 L kg^?1, and Cl_TB was 0.0096 ± 0.0024 L kg^?1 minute^?1. Extrapolated C₀ of butorphanol after IV administration was 146.5 ± 49.8 ng mL^?1. Estimated C_MAX after IM administration of butorphanol was 54.98 ± 14.60 ng mL^?1, and T_MAX was 16.2 ± 5.2 minutes; bioavailability was 82 ± 41%. Elimination half‐life of butorphanol was 1.87 ± 1.49 and 2.75 ± 1.93 hours for IV and IM administration, respectively. Goats became hyperactive after butorphanol administration within the first 5 minutes after administration. Behavioral scores for goats were significantly different from baseline at 15 minutes after IV administration and at 15 and 30 minutes after IM administration. Both time and plasma butorphanol concentration were predictors of behavior. Behavioral scores of all goats had returned to baseline by 120 minutes after IV administration and by 240 minutes after IM administration. Conclusions and Clinical Relevance The dose of butorphanol (0.1 mg kg^?1, IV or IM) being used clinically to treat postoperative pain in goats has an elimination half‐life of 1.87 and 2.75 hours, respectively. Nonpainful goats become transiently excited after IV and IM administration of butorphanol. Clinical trials to validate the efficacy of butorphanol as an analgesic in goats are needed.     

Pharmacokinetics of enrofloxacin and danofloxacin in premature calves

The aim of this study was to determine the pharmacokinetics/pharmacodynamics of enrofloxacin (ENR) and danofloxacin (DNX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. The study was performed on twenty‐four calves that were determined to be premature by anamnesis and general clinical examination. Premature calves were randomly divided into four groups (six premature calves/group) according to a parallel pharmacokinetic (PK) design as follows: ENR‐IV (10 mg/kg, IV), ENR‐IM (10 mg/kg, IM), DNX‐IV (8 mg/kg, IV), and DNX‐IM (8 mg/kg, IM). Plasma samples were collected for the determination of tested drugs by high‐pressure liquid chromatography with UV detector and analyzed by noncompartmental methods. Mean PK parameters of ENR and DNX following IV administration were as follows: elimination half‐life (t_1/2λz) 11.16 and 17.47 hr, area under the plasma concentration–time curve (AUC_0‐48) 139.75 and 38.90 hr*µg/ml, and volume of distribution at steady‐state 1.06 and 4.45 L/kg, respectively. Total body clearance of ENR and DNX was 0.07 and 0.18 L hr^?1 kg^?1, respectively. The PK parameters of ENR and DNX following IM injection were t_1/2λz 21.10 and 28.41 hr, AUC_0‐48 164.34 and 48.32 hr*µg/ml, respectively. The bioavailability (F) of ENR and DNX was determined to be 118% and 124%, respectively. The mean AUC_0‐48CPR/AUC_0‐48ENR ratio was 0.20 and 0.16 after IV and IM administration, respectively, in premature calves. The results showed that ENR (10 mg/kg) and DNX (8 mg/kg) following IV and IM administration produced sufficient plasma concentration for AUC_0‐24/minimum inhibitory concentration (MIC) and maximum concentration (C_max)/MIC ratios for susceptible bacteria, with the MIC₉₀ of 0.5 and 0.03 μg/ml, respectively. These findings may be helpful in planning the dosage regimen for ENR and DNX, but there is a need for further study in naturally infected premature calves.     

Development of a multiroute physiologically based pharmacokinetic model for orbifloxacin in rabbits

To predict the orbifloxacin concentrations in rabbits after multiple routes of administration, a flow‐limited multiroute physiologically based pharmacokinetic (PBPK) model was developed. Three routes of administration (IV, IM, and PO) were incorporated into this model. Physiological parameters including tissue weights and blood flows through different tissues were obtained from the literature. The tissue/plasma partition coefficients (P_Xs) for noneliminating tissues were calculated according to the area method, while the P_Xs for kidney and the rest of the body compartment, together with other parameters for absorption and elimination, were optimized based on the published concentrations. The comparisons between predicted and observed orbifloxacin concentrations proved its validity, and the present model predicted available concentration data well, including those in liver, kidney, muscle, lung, heart, and plasma after oral, intravenous, or intramuscular administration. A local sensitivity analysis was also performed, which showed that the parameters for oral absorption were most influential on the orbifloxacin concentrations. This model was used to predict plasma and tissue concentrations after multiple oral or intramuscular administration. This study demonstrated the feasibility of predicting drug residues in minor species after multiple routes of administration in the extra‐label manner using the PBPK modeling.     

Pharmacokinetics of dexamethasone following intra‐articular,intravenous, intramuscular,and oral administration in horses and its effects on endogenous hydrocortisone

Soma, L. R., Uboh, C. E., Liu, Y., Li, X., Robinson, M .A., Boston, R. C., Colahan, P. T. Pharmacokinetics of dexamethasone following intra‐articular, intravenous, intramuscular, and oral administration in horses and its effects on endogenous hydrocortisone. J. vet. Pharmacol. Therap.  36 , 181–191. This study investigated and compared the pharmacokinetics of intra‐articular (IA) administration of dexamethasone sodium phosphate (DSP) into three equine joints, femoropatellar (IAS), radiocarpal (IAC), and metacarpophalangeal (IAF), and the intramuscular (IM), oral (PO) and intravenous (IV) administrations. No significant differences in the pharmacokinetic estimates between the three joints were observed with the exception of maximum concentration (C_max) and time to maximum concentration (T_max). Median (range) C_max for the IAC, IAF, and IAS were 16.9 (14.6–35.4), 23.4 (13.5–73.0), and 46.9 (24.0–72.1) ng/mL, respectively. The T_max for IAC, IAF, and IAS were 1.0 (0.75–4.0), 0.62 (0.5–1.0), and 0.25 (0.08–0.25) h, respectively. Median (range) elimination half‐lives for IA and IM administrations were 3.6 (3.0–4.6) h and 3.4 (2.9–3.7) h, respectively. A 3‐compartment model was fitted to the plasma dexamethasone concentration–time curve following the IV administration of DSP; alpha, beta, and gamma half‐lives were 0.03 (0.01–0.05), 1.8 (0.34–2.3), and 5.1 (3.3–5.6) h, respectively. Following the PO administration, the median absorption and elimination half‐lives were 0.34 (0.29–1.6) and 3.4 (3.1–4.7) h, respectively. Endogenous hydrocortisone plasma concentrations declined from a baseline of 103.8 ± 29.1–3.1 ± 1.3 ng/mL at 20.0 ± 2.7 h following the administration of DSP and recovered to baseline values between 96 and 120 h for IV, IA, and IM administrations and at 72 h for the PO.     

Pharmacokinetics of ciprofloxacin in carp, African catfish and rainbow trout

The plasma disposition of ciprofloxacin was studied in carp, African catfish and trout after intravenous (IV) and intramuscular (IM) administration at a dose rate of 15 mg/kg. Pharmacokinetic analysis of IV data showed that ciprofloxacin was well distributed (distribution volume Vd(area): 3.08-5.59 litre/kg) and exhibited a similar elimination half-life of about 14 h in these 3 fish species. After IM administration to carp and trout a rapid absorption was noticed; the maximum ciprofloxacin plasma concentrations (mean: 3.49 and 2.37 micrograms/ml, respectively), were achieved within 1 h after injection. At the dose level applied, ciprofloxacin has potential therapeutic value for 2-5 days especially against gram-negative bacterial fish pathogens.     

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 and intramuscular bioavailability of difloxacin in dromedary camels (Camelus dromedarius)

Single-dose disposition kinetics of difloxacin (5mg/kg bodyweight) were determined in clinically normal male dromedary camels (n=6) following intravenous (IV) and intramuscular (IM) administration. Difloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. The concentration-time data were analysed by compartmental and non-compartmental kinetic methods. Following a single IV injection, the plasma difloxacin concentration-time curve was best described by a two-compartment open model, with a distribution half-life (t(1/2alpha)) of 0.22+/-0.02h and an elimination half-life (t(1/2beta)) of 2.97+/-0.31h. Steady-state volume of distribution (V(dss)) and total body clearance (Cl(tot)) were 1.02+/-0.21L/kg and 0.24+/-0.07L/kg/h, respectively. Following IM administration, the absorption half-life (t(1)(/)(2ab)) and the mean absorption time (MAT) were 0.44+/-0.03h and 1.53+/-0.22h, respectively. The peak plasma concentration (C(max)) of 2.84+/-0.34microg/mL was achieved at 1.42+/-0.21h. The elimination half-life (t(1/2el)) and the mean residence time (MRT) was 3.46+/-0.42h and 5.61+/-0.23h, respectively. The in vitro plasma protein binding of difloxacin ranged from 28-43% and the absolute bioavailability following IM administration was 93.51+/-11.63%. Difloxacin could be useful for the treatment of bacterial infections in camels that are sensitive to this drug.     

Pharmacokinetics of oxytetracycline after intramuscular administration with lidocaine in sheep, comparison with a conventional formulation

The pharmacokinetic behaviour of oxytetracycline (OTC) was studied in 11 sheep after intravenous and intramuscular administration at a single dosage of 20 mg kg⁻¹ bodyweight. A conventional formulation was injected by the intravenous route and two different preparations were administered by the intramuscular route: a conventional formulation (T-100) and an aqueous solution of OTC with lidocaine (1 per cent) (OTC-Q. The objective was to determine whether there are differences between both formulations in the disposition kinetics of OTC after intramuscular administration to sheep. After intravenous administration of the conventional formulation, plasma oxytetracycline concentrations were best fitted to an open two-compartment model. Mean apparent volume of distribution was 0·77±0·02 litre kg⁻¹ and the harmonic mean half-life was three hours. The OTC transfer process between central and peripheral compartments was fast and that did not influence the elimination process. After intramuscular administrations of both formulations, half-lives were longer than after intravenous administration (mean values of 14·1 and 58·2 hours for T-100 and OTC-L respectively). In both cases, a biphasic absorption, a ‘flip-flop’ model and a complete bioavailability were found. OTC-L provided therapeutic plasma concentrations over 0·5 μg ml⁻¹ (the minimum inhibitory concentration for most susceptible pathogens) for a longer period of time than T-100 (72 hours compared with 36 or 48 hours).     

Pharmacokinetic and pharmacodynamic modelling of intravenous,intramuscular and subcutaneous buprenorphine in conscious cats

ObjectiveTo describe simultaneous pharmacokinetics (PK) and thermal antinociception after intravenous (IV), intramuscular (IM) and subcutaneous (SC) buprenorphine in cats.Study designRandomized, prospective, blinded, three period crossover experiment.AnimalsSix healthy adult cats weighing 4.1 ± 0.5 kg.MethodsBuprenorphine (0.02 mg kg^?1) was administered IV, IM or SC. Thermal threshold (TT) testing and blood collection were conducted simultaneously at baseline and at predetermined time points up to 24 hours after administration. Buprenorphine plasma concentrations were determined by liquid chromatography tandem mass spectrometry. TT was analyzed using anova (p < 0.05). A pharmacokinetic-pharmacodynamic (PK-PD) model of the IV data was described using a model combining biophase equilibration and receptor association-dissociation kinetics.ResultsTT increased above baseline from 15 to 480 minutes and at 30 and 60 minutes after IV and IM administration, respectively (p < 0.05). Maximum increase in TT (mean ± SD) was 9.3 ± 4.9 °C at 60 minutes (IV), 4.6 ± 2.8 °C at 45 minutes (IM) and 1.9 ± 1.9 °C at 60 minutes (SC). TT was significantly higher at 15, 60, 120 and 180 minutes, and at 15, 30, 45, 60 and 120 minutes after IV administration compared to IM and SC, respectively. IV and IM buprenorphine concentration-time data decreased curvilinearly. SC PK could not be modeled due to erratic absorption and disposition. IV buprenorphine disposition was similar to published data. The PK-PD model showed an onset delay mainly attributable to slow biophase equilibration (t_1/2k_e0 = 47.4 minutes) and receptor binding (k_on = 0.011 mL ng^?1 minute^?1). Persistence of thermal antinociception was due to slow receptor dissociation (t_1/2k_off = 18.2 minutes).Conclusions and clinical relevanceIV and IM data followed classical disposition and elimination in most cats. Plasma concentrations after IV administration were associated with antinociceptive effect in a PK-PD model including negative hysteresis. At the doses administered, the IV route should be preferred over the IM and SC routes when buprenorphine is administered to cats.