Pharmacokinetics of pradofloxacin and doxycycline in serum, saliva, and tear fluid of cats after oral administration

The pharmacokinetic properties of pradofloxacin and doxycycline were investigated in serum, saliva, and tear fluid of cats. In a crossover study design, six cats were treated orally with a single dose of pradofloxacin (Veraflox^® Oral Suspension 2.5%) and doxycycline (Ronaxan^® 100 mg) at 5 mg/kg body weight. Following administration, samples of serum, saliva, and tear fluid were taken in regular intervals over a period of 24 h and analysed by turbulent flow chromatography/tandem mass spectrometry. All values are given as mean ± SD. Pradofloxacin reached a mean maximum serum concentration ( C _max) of 1.1 ± 0.5 μg/mL after 1.8 ± 1.3 h ( t _max). In saliva and tear fluid, mean C _max was 6.3 ± 7.0 and 13.4 ± 20.9 μg/mL, respectively, and mean t _max was 0.5 ± 0 and 0.8 ± 0.3 h, respectively. Doxycycline reached a mean C _max in serum of 4.0 ± 0.8 μg/mL after 4.3 ± 3.2 h. Whilst only at two time-points doxycycline concentrations close to the limit of quantification were determined in tear fluid, no detectable levels were found in saliva. The high concentrations of pradofloxacin in saliva and tear fluid are promising to apply pradofloxacin for the treatment of conjunctivitis and upper respiratory tract infections in cats. As doxycycline is barely secreted into these fluids after oral application the mechanisms of its clinical efficacy remain unclear.     

Investigation of pharmacokinetic parameters of tiamulin after intramuscular and subcutaneous administration in normal dogs

Laber, G. Investigation of pharmacokinetic parameters of tiamulin after intramuscular and subcutaneous administration in normal dogs. J. vet. Pharmacol. Therap. 11 , 45–49.
Kinetic variables for tiamulin in the normal dog have been determined. Serum concentrations of tiamulin were compared after intramuscular (i.m.) and subcutaneous (s.c.) administration of a single dose of tiamulin. Following a single i.m. dose of 10 mg/kg body weight, the compound was calculated to have a C_max= 0.61 ± 0.15 μg/ml, a T _max= 6 h and a t _½= 4.7 ± 1.4 h. Tiamulin showed dose-dependent pharmacokinetics when given as a single s.c. dose of either 10 mg or 25 mg/kg body weight. For the lower dose, the values C_max= 1.55 ± 0.11 μg/ml, T _max= 8 h and 1 _max= 4.28 ± 0.18 h were obtained. For the higher dose C _max= 3.14 ± 0.04 μg/ml, T _max= 8 h and t _½= 12.4 ± 3.4 h were calculated. When tiamulin was administered subcutaneously at a dose rate of 10 mg/kg body weight, higher and better maintained serum levels were achieved than those following i.m. administration. After repeated s.c. doses no significant accumulation of tiamulin occurred. Assuming that a continuous effective serum concentration is necessary throughout the course of therapy, these data would indicate that tiamulin should be given every 24 h.     

Disposition of metronidazole in hens (Gallus gallus) and quails (Coturnix coturnix japonica): pharmacokinetics and whole-body autoradiography

Hens were given single intravenous or oral doses (30 mg/kg body weight) of metronidazole and the plasma concentrations of the drug were determined by high-performance liquid chromatography (HPLC) at intervals from 10 min to 24 h after drug administration. Pharmacokinetic variables were calculated by the Lagrange algorithm technique. The elimination half-life ( t _1/2β) after the intravenous injection was 4.2 ± 0.5 h, the volume of distribution ( V _d(ss)) 1.1±0.2 L/kg and the total body clearance ( Cl _B) 131.2 ± 20 mL/h.kg. Oral bioavailability of the metronidazole was 78 ± 16%. The plasma maximum concentration ( C _max) 31.9 ± 2.3 μg/mL was reached 2 h after the oral administration and the oral elimination half-life ( t ₁/2β) was 4.7 ± 0.2 h. The binding of metronidazole to proteins in hen plasma was very low (less than 3%). Whole body autoradiography of [³H] metronidazole in hens and quails showed an even distribution of labelled material in various tissues at short survival intervals (1-4 h) after oral or intravenous administration. A high labelling was seen in the contents of the small and large intestines. In the laying quails a labelling was also seen in the albumen and in a ring in the periphery of the yolk at long survival intervals. Our results show that a concentration twofold above the MIC is maintained in the plasma of hens for at least 12 h at an oral dose of 30 mg/kg metronidazole.     

Pharmacokinetics and tissue residues of norfloxacin and its N-desethyl- and oxo-metabolites in healthy pigs

The pharmacokinetic properties of norfloxacin were determined in healthy pigs after single intramuscular (i.m.) and intravenous (i.v.) dosage of 8 mg/kg body weight After i.m. and i.v. administration, the plasma concentration-time graph was characteristic of a two-compartment open model. After single i.m. administration, norfloxacin was absorbed rapidly, with a t _max of 1.46 ± 0.06 h. The elimination half-life ( t _1/2β) and the mean residence time of norfloxacin in plasma were 4.99 ± 0.28 and 6.05 ± 0.22 h, respectively, after i.m. administration and 3.65 ± 0.16 and 3.34 ± 0.16 h, respectively, after i.v. administration. Intramuscular bioavailability was found to be 53.7 ± 4.4%. Plasma concentrations greater than 0.2 μg/mL were achieved at 20 min and persisted up to 8 h post-administration. Maximal plasma concentration was 1.11 ± 0.03 μg/mL. Statistically significant differences between the two routes of administration were found for the half-lives of both distribution and elimination phases ( t _1/2α, t _1/2β) and apparent volume of distribution (V_d(area)). In pigs, norfloxacin was mainly converted to desethylenenorfloxacln and oxonorfloxacin. Considerable tissue concentrations of norfloxacin, desethylenenorfloxacin, and oxonorfloxacin were found when norfloxacin was administered intramuscularly (8 mg/kg on 4 consecutive days). The concentration of the parent fluoroquinolone in liver and kidney ranged between 0.015 and 0.017 μg/g on day 12 after the end of dosing.     

Pharmacokinetics and bioequivalence of parenterally administered doramectin in cattle

Plasma concentrations of doramectin in 40 cattle dosed by subcutaneous (sc) or intramuscular (i.m.) injection (200 μg/kg) were compared to assess the bioequivalence of the two routes of administration. Peak concentration ( C _max), and areas under the concentration curve ( AUC_0– ) were determined from plasma concentrations. Animals treated by the sc route showed a mean AUC_0– of 457 ± 66 ng±day/mL (± SD) and a mean C _max of 27.8 ± 7.9 ng/mL. Results from the i.m. treatment group showed a mean AUC _0– of 475 ± 82 ng-day/mL and a mean C _max of 33.1 ± 9.0 ng/mL Absorption constants ( k _a) determined by modelling were 0.542 ± 0.336 day^-1after sc administration and 0.710 ± 0.357 day^-1after i.m. administration. The 90% confidence limits on the difference between mean AUC _0– values for the sc and i.m. groups fell within 20% of the mean value for the subcutaneous group. C _max was somewhat greater for the i.m. route. The 90% confidence limits on the difference in mean In ( T _max+1) also fell within 20% of the mean sc value. Based on this analysis, bioequivalence of the sc and i.m. formulation has been established.     

Pharmacokinetics of dirlotapide in the dog

An overview of the pharmacokinetics of dirlotapide in beagle dogs is presented. The following mean parameters were observed after a 0.3-mg/kg i.v. dose of dirlotapide: plasma clearance of 7.8 mL/min/kg and volume of distribution of 1.3 L/kg. Following single oral doses of 0.05, 0.3, and 1.0 mg/kg to fed dogs and 0.3 mg/kg to fasted dogs using the commercial formulation, mean C _max of 7.5, 46, 97, and 31 ng/mL, respectively, were observed at mean t _max of 0.8–2.0 h. AUC and C _max increased with increasing dose, but not proportionally. Oral bioavailability was 22–41%. Exposure, as reflected by AUC , was 54% higher in the fed than fasted state. In a 14-day repeated-dose study (0.3 mg/kg dose), the mean accumulation ratio was 3.7. In a 3-month study at doses of 0.4–2.5 mg/kg, accumulation ratios ranged from 2.0 to 6.7 at day 29 and from 1.3 to 4.1 at day 87. In summary, dirlotapide exhibited low clearance, low first-pass metabolism, moderate volume of distribution, low-to-moderate oral bioavailability, a modest food effect, and variable accumulation. Large interanimal variability in systemic exposure was noted for all routes and doses, but there were no consistent sex differences.     

Single and multiple-dose pharmacokinetics of tepoxalin and its active metabolite after oral administration to rabbits (Oryctolagus cuniculus)

The anti-inflammatory agent, tepoxalin, was administered to eight healthy 6-month-old female New Zealand white rabbits once daily at an oral dose of 10 mg/kg. Blood samples were obtained immediately before and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 h postadministration on days 1 and 10. Tepoxalin and its active metabolite, RWJ 20142, concentrations were determined in plasma by use of high-performance liquid chromatography with mass spectrometry. C _max of the parent compound was reached between 3 and 8 h of drug administration, with a harmonic mean t _1/2 of 3.6 h. Peak tepoxalin plasma concentrations were 207 ± 49 ng/mL. After oral administration, the metabolite RWJ 20142 achieved C _max in plasma 2–8 h after administration, with a t _1/2 of 1.9–4.8 h (harmonic mean 2.8 h). Peak plasma concentrations of RWJ 20142 on day 1 were 2551 ± 1034 ng/mL.     

Pharmacokinetics of a new long acting endectocide formulation containing 2.25% ivermectin and 1.25% abamectin in cattle

The objective of this study was to determine the kinetic parameters of a new formulation that contained 2.25% ivermectin combined with 1.25% abamectin in bovine plasma. The results for 2.25% ivermectin: C _max (37.11 ng/mL ± 7.42), T _max (16 days ± 5.29), T _1/2 (44.62 days ± 53.89), AUC (928.2 ng·day/mL ± 153.83) and MRT (36.73 days ± 33.64), and for 1.25% abamectin: C _max (28.70 ng/mL ± 9.54), T _max (14 days ± 4.04), T _1/2 (15.40 days ± 11.43), AUC (618.05 ng·day/mL ± 80.27) and MRT (20.79 days ± 8.43) suggest that this combination of 2.25% ivermectin + 1.25% abamectin possesses properties that give this pharmaceutical formula a longer activity time than two of the commercial products tested (1% ivermectin and 1% abamectin), and showed similarity to 3.15% ivermectin.     

Plasma pharmacokinetics and urine concentrations of meropenem in ewes

The pharmacokinetics of meropenem was studied in five ewes after single i.v. and i.m. dose of 20 mg/kg bw. Meropenem concentrations in plasma and urine were determined using microbiological assay method. A two-compartment open model was best described the decrease of meropenem concentration in plasma after an i.v. injection. The drug was rapidly eliminated with a half-life of elimination ( t _{1/2 β} ) of 0.39 ± 0.30 h. Meropenem showed a small steady-state volume of distribution [ V _d(ss)] 0.055 ± 0.09 L/kg. Following i.m. injection, meropenem was rapidly absorbed with a t _1/2ab of 0.25 ± 0.04 h. The peak plasma concentration ( C _max) was 48.79 ± 8.83  μ g/mL was attained after 0.57 ± 0.13 h ( t _max). The elimination half-life ( t _1/2el) of meropenem was 0.71 ± 0.12 h and the mean residence time ( MRT ) was 1.38 ± 0.26 h. The systemic bioavailability (F) after i.m. injection was 112.67 ± 10.13%. In vitro protein-binding percentage of meropenem in ewe's plasma was 42.80%. The mean urinary recoveries of meropenem over 24 h were 83% and 91% of the administered dose after i.v. and i.m. injections respectively. Thus, meropenem is likely to be efficacious in the eradication of many urinary tract pathogens in sheep.     

Bioavailability and pharmacokinetics of ibuprofen in the broiler chicken

The intravenous, intramuscular and oral pharmacokinetics of ibuprofen in broiler chickens were investigated. In a preliminary study, plasma ibuprofen concentration-time profiles, following i.v. (25 mg/kg) dosing were best described by a 2-compartment model. After intravenous administration, the volume of distribution at steady-state ( V _d(ss)), the total systemic clearance ( Cl _B), the elimination half-life (t_1/2p) and the MRT were 0.303 L/kg, 482.3 ml/h-kg, 2.71 h and 1.02 h, respectively. After intramuscular administration of ibuprofen, the t _max and C _max were 0.37 h, and 42.2μg/mL, respectively, with an estimated bioavailability of 46.7%. After oral administration of ibuprofen, the t _max and C _max were 0.31 h and 23.91 μg/mL, respectively, with an estimated bioavailability of 24.2%. This is a preliminary study, examining the use of ibuprofen in broiler chickens, and should be followed by tissue residue and efficacy studies in different disease states.     

Disposition and bioavailability of neomycin in Holstein calves

Pedersoli, W.M., Ravis, W.R., Jackson, J., Shaikh, B. Disposition and bioavailability of neomycin in Holstein calves. J. vet. Pharmacol. Therap. 17 , 5–11.
The disposition and absorption kinetics of neomycin were studied in healthy ruminating dairy calves ( n -6), approximately 3-months-old. The calves were treated with single intravenous (i.v.) (12 mg/kg), intramuscular (i.m.) (24mg/kg), oral (p.o.) (96 mg/kg) and repeated p.o. (96 mg/kg, b.i.d., 15½ days) doses of neomycin. A 3-week rest period was allowed between treatments A and B and B and C Baseline and serial venous blood samples were collected from each calf plasma concentrations of neomycin were determined by a high performance liquid chromatography procedure. The resulting data were evaluated by using compartmental pharmacokinetic models and nonlinear least squares regression analysis. The mean of some selected parameters were t ½λ3 7.48 ± 2.02 h, Cl_t= 0.25 ± 0.04 L/h/kg, V _d(ss)= 1.17 ± 0.23 L/kg, and MRT = 4.63 ± 0.87 h for the i.v. data and t _½= 11.5 ± 3.8 h, MRT _abs= 0.960 ± 1.001 h, F = 127 ± 35.2%, and Cl_t/F = 0.199 ± 0.047 L/h/kg for the i.m. data, respectively. Only one calf absorbed neomycin to any significant degree (F = 0.0042) after a single p.o. dose. Selected mean parameters determined after repeated oral dosing were: F = 0.45 ± 0.45%, C_max= 0.26 ± 0.37 g/ml, and t_max= 2.6 ± 2.9 h. Terminal half-lives determined for the i.v. and i.m. treatments were considerably longer than those reported previously in the literature.     

Bioavailability of amprolium in fasting and nonfasting chickens after intravenous and oral administration

The bioavailability of amprolium (APL) was measured after intravenous (i.v.) and oral (p.o.) administration to chickens. Twelve healthy chickens weighing 1.28–1.41 kg received a dose of 13 mg APL/kg intravenously, and 13 or 26 mg APL/kg orally in both a fasted and a nonfasted condition in a Latin square design. Plasma samples were taken from the subwing vein for determination of APL concentration by HPLC method. The data following intravenous and oral administration were best fitted by 2-compartment and 1-compartment models, respectively, using weighted nonlinear least squares regression. The half-life beta t _½β, volume of distribution ( V d) and total body clearance ( Cl ) after intravenous administration were 0.21 h, 0.12 L/kg and 1.32 L/h.kg, respectively. The elimination half-life ( t _½ K_el) after oral administration was 0.292–0.654 h which is 1.5–3.2 times longer than after intravenous administration, suggesting the presence of a 'flip-flop' phenomenon in chickens. The maximum plasma concentration ( C _max) of 13 mg/kg APL administered orally to chickens during fasting was significantly (about four times) higher than that during nonfasting ( P < 0.05). Bioavailability during nonfasting was from 2.3 to 2.6%, and 6.4% during fasting.     

The pharmacokinetics of clomipramine and desmethylclomipramine in dogs: parameter estimates following a single oral dose and 28 consecutive daily oral doses of clomipramine

Clomipramine is a tricyclic antidepressant that has been recommended for the treatment of canine compulsive disorder. The pharmacokinetics of clomipramine in dogs have not been reported. This study describes the pharmacokinetics of clomipramine and its active metabolite, desmethylclomipramine, in six male dogs. Serial blood samples were collected following both a single oral dose of clomipramine (3 mg/kg) and 28 consecutive daily oral doses (3 mg/kg q 24 h). In addition, 'peak' and 'trough' samples were taken throughout the 28-day dosing period. Plasma was assayed for total (free and protein-bound) clomipramine and desmethylclomipramine, using gas-chromatography with mass spectrometric detection. Various pharmacokinetic parameters were then determined. Following a single dose of clomipramine, time of maximum plasma concentration ( t _max) of clomipramine was 0.75–3.1 h, maximum plasma concentration ( C _max) was 16–310 ng/mL and elimination half-life ( t _1/2el) was 1.2–16 h; t _max of desmethylclomipramine was 1.4–8.8 h, C _max was 21–134 ng/mL and t _1/2el was 1.2–2.3 h. Following multiple dosing, there was a numeric increase in these parameters; t _max of clomipramine was 3–8 h, C _max was 43–222 ng/mL and t _1/2el was 1.2–16 h; t _max of desmethylclomipramine was 1.4–8.8 h, C _max was 21–134 ng/mL and t _1/2el was 1.2–2.3 h. Clinically significant differences between dogs and humans in the pharmacokinetics of oral clomipramine are discussed.     

Pharmacokinetics of valacyclovir in the adult horse

Recent outbreaks of equine herpes virus type-1 infections have stimulated renewed interest in the use of effective antiherpetic drugs in horses. The purpose of this study was to investigate the pharmacokinetics of valacyclovir (VCV), the prodrug of acyclovir (ACV), in horses. Six adult horses were used in a randomized cross-over design. Treatments consisted of 10 mg/kg ACV infused intravenously, 5 g (7.7–11.7 mg/kg) VCV delivered intragastrically (IG) and 15 g (22.7–34.1 mg/kg) VCV administered IG. Serum samples were obtained at predetermined times for acyclovir assay using high-performance liquid chromatography. Following the administration of 5 g VCV, the mean observed maximum serum ACV concentration ( C _max) was 1.45 ± 0.38 (SD) μg/mL, at 0.74 ± 0.43 h. At a dose of 15 g VCV, the mean C _max was 5.26 ± 2.82 μg/mL, at 1 ± 0.27 h. The mean bioavailability of ACV from oral VCV was 60 ± 12% after 5 g of VCV and 48 ± 12% after 15 g VCV, and did not differ significantly between dose rates ( P  > 0.05). Superposition suggested that a loading dose of 27 mg/kg VCV every 8 h for 2 days, followed by a maintenance dose of 18 mg/kg every 12 h, will maintain effective serum ACV concentrations.     

Pharmacokinetics of indomethacin in sheep after intravenous and intramuscular administration

The pharmacokinetics of indomethacin (1mg/kg) was determined in six adult sheep after intravenous (i.v.) and intramuscular (i.m.) injection. Plasma concentrations were maintained within the therapeutic range (0.3–3.0 μg/mL) from 5 to 50 min after i.v. and from 5 to 60–90 min after i.m. administration. After two trials, indomethacin best fitted an open two-compartment model. The mean (±SD) volumes of distribution at steady state ( V d_ss) were 4.10 ± 1.40 and 4.21 ± 1.93 L/kg and the mean clearance values ( C l_B) were 0.17 ± 0.06 and 0.22 ± 0.12 L/h.kg for i.v. and i.m. routes, respectively. The elimination phase half-lives did not show any significant difference between routes of injection ( t _½β = 17.4 ± 4.6 and 21.25 ± 4.44 h, i.v. and i.m. respectively). After i.m. administration, plasma maximum concentration ( C _max =  1.10 ± 0.68 μg/mL) was reached 10 min after dosing; the absorption phase was fast ( K _ab = 26 ± 18 h-1) and short ( t _½ab = 2.33 ± 1.51 min) and the mean bioavailability was 91.0 ± 32.8%, although there was considerable interanimal variation. In some individuals, bioavailability was higher than 100%. This fact combined with the slower elimination phase after i.m. than after i.v. administration, could be related with enterohepatic recycling.     

In vitro kinetics of hepatic albendazole sulfoxidation in channel catfish (Ictalurus punctatus), tilapia (Oreochromis sp.), rainbow trout (Oncorhynchus mykiss) and induction of EROD activity in ABZ-dosed channel catfish

Liver microsomes from market-size ( n  = 6) rainbow trout, channel catfish and tilapia were used to investigate in vitro biotransformation kinetics of albendazole (ABZ). ABZ was transformed to a single metabolite, ABZ sulfoxide (ABZ-SO). Catfish displayed the highest maximal velocity ( V _max = 264.0 ± 58.6 pmols ABZ-SO/min/mg protein) followed by tilapia (112.3 ± 8.2) and rainbow trout (73.3 ± 10.3). V _max in catfish was significantly different ( P  < 0.05) from the other two species. Michaelis–Menten constant ( K _m) values (μ m ) varied significantly among the species: rainbow trout (3.9 ± 0.5), tilapia (9.2 ± 1.7) and catfish (22.0 ± 3.2). However, V _max/ K _m ratios showed no difference among the three species, making them equally efficient performing this phase I biotransformation reaction. In a second series of experiments, channel catfish ( n  = 6 per treatment) were dosed in vivo with gel-food containing ABZ (10 mg/kg, p.o.). Fish were killed at 24, 48, 72 and 120 h after dosage. Control fish were fed ABZ-free feed. Induction of ethoxyresorufin-o-deethylase activity was significant ( P  < 0.05) in all ABZ-dosed treatments as compared with controls.     

Pharmacokinetics, bioavailability and dosage regimen of sulphadiazine (SDZ) in camels (Camelus dromedarius)

The pharmacokinetics of sulphadiazine (SDZ) (100 mg/kg, body weight) were investigated in six camels ( Camelus dromedarius ) after intravenous (i.v.) and oral (p.o.) administration. Following i.v. administration, the overall elimination rate constant (β) was 0.029±0.001/h and the half-life ( t _½β) was 23.14±1.06 h. The apparent volume of distribution ( V d_(area)) was 0.790±0.075 L/kg and the total body clearance ( Cl _B) was 23.29±2.50 mL/h/kg. After p.o. administration, SDZ reached a peak plasma concentration ( C _max(cal.)) of 62.93±2.79 μg/mL at a post injection time of ( T _max(cal.)) 22.98±0.83 h. The elimination half-life was 19.79±1.22 h, not significantly different from that obtained by the i.v. route. The mean absorption rate constant (K_a) was 0.056±0.002 h⁻¹ and the mean absorption half-life ( t _½Ka) was 12.33±0.37 h. The mean availability ( F ) of sulphadiazine was 88.2±6.2%.
  To achieve and maintain therapeutically satisfactory plasma SDZ levels of 50 μg/mL, the priming and maintenance doses would be 80 mg/kg and 40 mg/kg intravenously and 90 mg/kg and 45 mg/kg orally, respectively, to be repeated at 24 h intervals.     

Influence of Pasteurella multocida infection on the pharmacokinetic behavior of marbofloxacin after intravenous and intramuscular administrations in rabbits

Abo-El-Sooud, K., Goudah, A. Influence of Pasteurella multocida infection on the pharmacokinetic behavior of marbofloxacin after intravenous and intramuscular administrations in rabbits. J. vet. Pharmacol. Therap. 33 , 63–68.
The pharmacokinetic behavior of marbofloxacin was studied in healthy ( n  = 12) and Pasteurella multocida infected rabbits ( n  = 12) after single intravenous (i.v.) and intramuscular (i.m.) administrations. Six rabbits in each group (control and diseased) were given a single dose of 2 mg/kg body weight (bw) of marbofloxacin intravenously. The other six rabbits in each group were given the same dose of the drug intramuscularly. The concentration of marbofloxacin in plasma was determined using high-performance liquid chromatography. The plasma concentrations were higher in diseased rabbits than in healthy rabbits following both routes of injections. Following i.v. administration, the values of the elimination half-life ( t _1/2β), and area under the curve were significantly higher, whereas total body clearance was significantly lower in diseased rabbits. After i.m. administration, the elimination half-life ( t _1/2el), mean residence time, and maximum plasma concentration ( C _max) were higher in diseased rabbits (5.33 h, 7.35 h and 2.24 μg/mL) than in healthy rabbits (4.33 h, 6.81 h and 1.81 μg/mL, respectively). Marbofloxacin was bound to the extent of 26 ± 1.3% and 23 ± 1.6% to plasma protein of healthy and diseased rabbits, respectively. The C _max /MIC (minimum inhibitory concentration) and AUC/MIC ratios were significantly higher in diseased rabbits (28 and 189 h) than in healthy rabbits (23 and 157 h), indicating the favorable pharmacodynamic characteristics of the drug in diseased rabbits.     

Bioavailability, pharmacokinetics, and tissue distribution of 14C homidium after parenteral administration to Boran cattle

The absorption, distribution and elimination characteristics of ¹⁴C homidium have been described in non-infected and Trypanosoma congolense -infected cattle treated with ¹⁴C homidium chloride by either intramuscular (i.m.) or intravenous (i.v.) injection at a dose level of 1 mg/kg body weight. Results show that the mean (± SD) elimination of the drug from plasma followed a biexponential process, with half-lives of 0.084 ± 0.006 h and 97.66 ± 16.28 h for the distribution and elimination phases after intravenous injection, respectively. Bioavailability of the intramuscular dose was 62.5% and 57.8% in non-infected and trypanosome-infected cattle, respectively. Absorption was rapid, with a t _max of 15 min and a mean C _max (± SD) of 268.4 ± 4.09 ng/mL following the intramuscular dose in non-infected cattle. The major route of excretion was via faeces. Approximately 90% of the total dose given to non-infected i.m.-treated cattle was excreted within 14 days. Following intramuscular administration of the drug, residues remained high in the major excretory organs, with the liver having concentrations of 1411 and 1199 ng/g after 14 and 28 days, respectively. Over the same period, the values in the kidneys were 649 and 448 ng/g. Concentrations in the liver 14 and 21 days following i.v. treatment were 2195 and 2454 ng/g, respectively. These results show that there was no significant difference in liver drug residues between 14 and 21 days, or 28 days depending on the treatment given, suggesting that once the drug is in this organ, it is released back into the circulation at an extremely slow rate.     

Pharmacokinetics of marbofloxacin in dogs after oral and parenteral administration

Six dogs were treated with a single intravenous (i.v.) dose (2 mg/kg) of marbofloxacin, followed by single oral (p.o.) doses of marbofloxacin at 1, 2 and 4 mg/kg, according to a three-way crossover design. The same experimental design was used for the subcutaneous (s.c.) route. In addition, a long-term trial involving eight dogs given oral doses of marbofloxacin at 2, 4 and 6 mg/kg/day for thirteen weeks was carried out. Plasma and urine samples were collected during the first two trials, plasma and skin samples were collected after the second of these trials. Plasma, urine and skin concentrations of marbofloxacin were determined by a reverse phase liquid chromatographic method. Mean pharmacokinetic parameters after i.v. administration were the following: t1/2β=12.4h; Cl _B= 0.10 L/h.kg; V _area= 1.9 L/kg. The oral bioavailability of marbofloxacin was close to 100% for the three doses. At 2 mg/kg, C _max of 1.4 μg/mL was reached at t _max of 2.5 h. Mean AUC and C _max values had a statistically significant linear relationship with the doses administered. About 40% of the administered dose was excreted in urine as unchanged parent drug. After s.c. administration, the calculated parameters were close to those obtained after oral administration, except t _max (about 1 h) which was shorter. The mean skin to plasma concentration ratio after the long-term trial was 1.6, suggesting good tissue penetration of marbofloxacin.