Pharmacokinetics of Amikacin in Lactating Sheep

The pharmacokinetics of amikacin (AMK) were investigated after intravenous (i.v.) and intramuscular (i.m.) administration of 7.5 mg/kg bw in 6 healthy lactating sheep. After i.v. AMK injection (as a bolus), the elimination half-life (t1/2beta), the volume of distribution (Vd,area), the total body clearance (ClB) and the area under the concentration-time curve (AUC) were 1.64 +/- 0.06 h, 0.19 +/- 0.02 L/kg, 1.36 +/- 0.1 ml/min per kg and 94.09 +/- 6.95 (microg.h)/ml, respectively. The maximum milk concentration of AMK (Cmax), the area under the milk concentration-time curve (AUCmilk) and the ratio AUCmilk/AUCserum were 1.18 +/- 0.22 microg/ml, 22.45 +/- 3.21 (micro.h)/ml and 0.24 +/- 0.02, respectively. After i.m. administration of AMK the t1/2beta, Cmax, time of Cmax (tmax) and absolute bioavailability (Fabs) were 1.29 +/- 0.1 h, 16.97 +/- 1.54 microg/ml, 1.0 +/- 0 h and 64.88% +/- 6.16%, respectively. The Cmax, AUCmilk and the ratio AUCmilk/AUCserum were 0.33 microg/ml, 1.67 (microg.h)/ml and 0.036, respectively.     

Pharmacokinetics of cefepime administered by i.v. and i.m. routes to ewes

The pharmacokinetics of cefepime were studied following i.v. and i.m. administration of 20 mg/kg in 10 ewes. Following i.v. administration of a single dose, the plasma concentration-time curves of cefepime were best fitted using a two-compartment open model. The elimination half-life (t(1/2beta)) was 1.76 +/- 0.07 h, volume of distribution at steady-state [V(d(ss))] was 0.32 +/- 0.01 L/kg and total body clearance (Cl(B)) was 2.37 +/- 0.05 mL/min.kg. Following i.m. administration, the drug was rapidly absorbed with an absorption half-life (t(1/2ab)) of 0.49 +/- 0.05 h, maximum plasma concentration (Cmax) of 31.9 +/- 1.5 mug/mL was attained at (tmax) 1.1 +/- 0.2 h and the drug was eliminated with an elimination half-life (t(1/2el)) of 2.06 +/- 0.11 h. The systemic bioavailability (F) after i.m. administration of cefepime was 86.8 +/- 7.5%. The extent of plasma protein binding measured in vitro was 14.8 +/- 0.54%. The drug was detected in urine for 36 h postadministration by both routes.     

Pharmacokinetics and bioavailability of nimesulide in goats

The pharmacokinetic properties and bioavailability of cyclooxygenase (COX)-2 selective nonsteroidal anti-inflammatory drug nimesulide were investigated in female goats following intravenous (i.v.) and intramuscular (i.m.) administration at a dose of 4 mg/kg BW. Blood samples were collected by jugular venipuncture at predetermined times after drug administration. Plasma concentrations of nimesulide were determined by a validated high-performance liquid chromatography method. Plasma concentration-time data were subjected to compartmental analysis and pharmacokinetic parameters for nimesulide after i.v. and i.m. administration were calculated according to two- and one-compartment open models respectively. Following i.v. administration, a rapid distribution phase was followed by the slower elimination phase. The half-lives during the distribution phase (t1/2alpha) and terminal elimination phase (t1/2beta) were 0.11+/-0.10 and 7.99+/-2.23 h respectively. The steady-state volume of distribution (Vd(ss)), total body clearance (ClB) and mean residence time (MRT) of nimesulide were 0.64+/-0.13 L/kg, 0.06+/-0.02 L/h/kg and 11.72+/-3.42 h respectively. After i.m. administration, maximum plasma concentration (Cmax) of nimesulide was 2.83+/-1.11 microg/mL attained at 3.6+/-0.89 h (tmax). Plasma drug levels were detectable up to 72 h. Following i.m. injection, the t1/2beta and MRT of nimesulide were 1.63 and 1.73 times longer, respectively, than the i.v. administration. The bioavailability of nimesulide was 68.25% after i.m. administration at 4 mg/kg BW. These pharmacokinetic data suggest that nimesulide given intramuscularly may be useful in the treatment of inflammatory disease conditions in goats.     

Pharmacokinetics of sarafloxacin in pigs and broilers following intravenous, intramuscular, and oral single-dose applications

Pharmacokinetics of sarafloxacin, a fluoroquinolone antibiotic, was determined in pigs and broilers after intravenous (i.v.), intramuscular (i.m.), or oral (p.o.) administration at a single dose of 5 (pigs) or 10 mg/kg (broilers). Plasma concentration profiles were analysed by a noncompartmental pharmacokinetic method. Following i.v., i.m. and p.o. doses, the elimination half-lives (t1/2beta) were 3.37 +/- 0.46, 4.66 +/- 1.34, 7.20 +/- 1.92 (pigs) and 2.53 +/- 0.82, 6.81 +/- 2.04, 3.89 +/- 1.19 h (broilers), respectively. After i.m. and p.o. doses, bioavailabilities (F) were 81.8 +/- 9.8 and 42.6 +/- 8.2% (pigs) and 72.1 +/- 8.1 and 59.6 +/- 13.8% (broilers), respectively. Steady-state distribution volumes (Vd(ss)) of 1.92 +/- 0.27 and 3.40 +/- 1.26 L/kg and total body clearances (ClB) of 0.51 +/- 0.03 and 1.20 +/- 0.20 L/kg/h were determined in pigs and broilers, respectively. Areas under the curve (AUC), mean residence times (MRT), and mean absorption times (MAT) were also determined. Sarafloxacin was demonstrated to be more rapidly absorbed, more extensively distributed, and more quickly eliminated in broilers than in pigs. Based on the single-dose pharmacokinetic parameters determined, multiple dosage regimens were recommended as: a dosage of 10 mg/kg given intramuscularly every 12 h in pigs, or administered orally every 8 h in broilers, can maintain effective plasma concentrations with bacteria infections, in which MIC90 are <0.25 microg/mL.     

Some pharmacokinetic data of aditoprim and trimethoprim in healthy and tick-borne fever infected dwarf goats

Aditoprim (AP) is a new dihydrofolate reductase inhibitor, which is structurally related to trimethoprim (TMP). The pharmacokinetics of AP (10 mg/kg) and TMP (20 mg/kg) were assessed in healthy dwarf goats. Therapeutic efficacy against rickettsial infections was tested in tick-borne fever (TBF) infected goats. The animals were given TMP (n = 5) or AP (n = 5) by i.v. injection, and subsequently the drugs were administered orally (same groups, similar doses). Finally, both groups were infected with TBF and the i.v. experiment was repeated. Plasma concentration-time curves for both drugs followed first-order two-compartment decay. For TMP, mean t1/2 beta +/- SEM (h) was 0.84 +/- 0.06 (i.v. control) and 0.90 +/- 0.06 (i.v. infected), respectively, whereas for AP values of 8.00 +/- 0.31 (i.v. control) and 10.28 +/- 0.67 (i.v. infected) were obtained (P less than 0.05). Mean Vd beta +/- SEM values (l/kg) were 3.84 +/- 0.27 (i.v. control) and 4.07 +/- 0.85 (i.v. infected) for TMP (NS) and 7.02 +/- 0.63 vs 9.29 +/- 0.21 (P less than 0.05) for AP. After i.v. injection, rumen fluid concentrations of AP were significantly (P less than 0.05) higher and more persistent than those of TMP. For AP, the plasma and rumen fluid concentrations at 3 h were 1.20 +/- 0.06 micrograms/ml and 0.85 +/- 0.17 microgram/ml, respectively. After oral administration of TMP, Cmax in plasma was 0.12 +/- 0.01 microgram/ml and the maximum was reached after 1.2 +/- 0.16 h; systemic bioavailability (F) was 10.3% (relative to AUC i.v.). Oral treatment with AP resulted in a Cmax value of 0.21 +/- 0.02 microgram/ml with Tmax of 22.5 +/- 1.65 h and a F value of 71%. Based on WBC, serum ALP and rectal temperature responses, it was concluded that both TMP and AP were inactive against Ehrlichia phagocytophila.     

Bioavailability and pharmacokinetics of florfenicol in healthy sheep

A study on bioavailability and pharmacokinetics of florfenicol was conducted in 20 crossbred healthy sheep following a single intravenous (i.v.) and intramuscular (i.m.) doses of 20 and 30 mg/kg body weight (b.w.). Florfenicol concentrations in serum were determined by a validated high-performance liquid chromatography method with UV detection at a wavelength of 223 nm in which serum samples were spiked with chloramphenicol as internal standard. Serum concentration-time data after i.v. administration were best described by a three-compartment open model with values for the distribution half-lives (T(1/2alpha)) 1.51 +/- 0.06 and 1.59 +/- 0.10 h, elimination half-lives (T(1/2beta)) 18.83 +/- 6.76 and 18.71 +/- 1.85 h, total body clearance (Cl(B)) 0.26 +/- 0.03 and 0.25 +/- 0.01 L/kg/h, volume of distribution at steady-state (V(d(ss))) 1.86 +/- 0.11 and 1.71 +/- 0.20 L/kg, area under curve (AUC) 76.31 +/- 9.17 and 119.21 +/- 2.05 microg.h/mL after i.v. injections of 20 and 30 mg/kg b.w. respectively. Serum concentration-time data after i.m. administration were adequately described by a one-compartment open model. The pharmacokinetic parameters were distribution half-lives (T(1/2k(a) )) 0.27 +/- 0.03 and 0.25 +/- 0.09 h, elimination half-lives (T(1/2k(e) )) 10.34 +/- 1.11 and 9.57 +/- 2.84 h, maximum concentrations (C(max)) 4.13 +/- 0.29 and 7.04 +/- 1.61 microg/mL, area under curve (AUC) 67.95 +/- 9.61 and 101.95 +/- 8.92 microg.h/mL, bioavailability (F) 89.04% and 85.52% after i.m. injections of 20 and 30 mg/kg b.w. respectively.     

Pharmacokinetics and endometrial tissue concentrations of enrofloxacin and the metabolite ciprofloxacin after i.v. administration of enrofloxacin to mares

Enrofloxacin was administered i.v. to five adult mares at a dose of 5 mg/kg. After administration, blood and endometrial biopsy samples were collected at regular intervals for 24 h. The plasma and tissue samples were analyzed for enrofloxacin and the metabolite ciprofloxacin by high-pressure liquid chromatography. In plasma, enrofloxacin had a terminal half-life (t(1/2)), volume of distribution (area method), and systemic clearance of 6.7 +/- 2.9 h, 1.9 +/- 0.4 L/kg, and 3.7 +/- 1.4 mL/kg/min, respectively. Ciprofloxacin had a maximum plasma concentration (Cmax) of 0.28 +/- 0.09 microg/mL. In endometrial tissue, the enrofloxacin Cmax was 1.7 +/- 0.5 microg/g, and the t(1/2) was 7.8 +/- 3.7 h. Ciprofloxacin Cmax in tissues was 0.15 +/- 0.04 microg/g and the t(1/2) was 5.2 +/- 2.0 h. The tissue:plasma enrofloxacin concentration ratios (w/w:w/v) were 0.175 +/- 0.08 and 0.47 +/- 0.06 for Cmax and AUC, respectively. For ciprofloxacin, these values were 0.55 +/- 0.13 and 0.58 +/- 0.31, respectively. We concluded that plasma concentrations achieved after 5 mg/kg i.v. are high enough to meet surrogate markers for antibacterial activity (Cmax:MIC ratio, and AUC:MIC ratio) considered effective for most susceptible gram-negative bacteria. Endometrial tissue concentrations taken from the mares after dosing showed that enrofloxacin and ciprofloxacin both penetrate this tissue adequately after systemic administration and would attain concentrations high enough in the tissue fluids to treat infections of the endometrium caused by susceptible bacteria.     

Comparative pharmacokinetics of enrofloxacin and ciprofloxacin in chickens

The pharmacokinetics of enrofloxacin (EFX) and ciprofloxacin (CFX) was investigated in broiler chickens. Each antimicrobial was administered intravenously at a dose of 5 mg/kg body weight. Blood was taken in different preset times: prior and at 0.03, 0.06, 0.13, 0.25, 0.5, 1, 2, 4, 8, 12 and 24 h following drug administration. The concentrations of EFX and CFX in plasma were determined by high pressure liquid chromatography (HPLC). Plasma concentrations vs. time were analysed by a compartmental independent pharmacokinetic model that provided the most important kinetic parameters. Statistically significant differences between the two antimicrobials were found for most of the pharmacokinetic parameters: Area under the curve (AUC), area under first moment curve (AUMC), mean residence time (MRT), total body cleareance (ClB), volume of distribution beta (Vd beta) and volume of distribution at the steady state (Vd(ss)). Both antimicrobials were widely distributed in chickens throughout the body with a mean Vd(ss) of 1.98+/-0.18 L/kg for EFX, and 4.04+/-0.69 L/kg for CFX. The ClB for CFX was five times higher than that obtained for EFX. AUC, MRT and the diminished half time for EFX were two-four times higher than those obtained for CFX. These results indicate that CFX remains in the body for less time than the other quinolone. This characteristic of CFX suggests the advantage of a shorter withdrawal time for food producing animals treated with this antimicrobial.     

Disposition Kinetics,Bioavailability and Renal Clearance of Cefepime in Calves

The pharmacokinetics of cefepime were studied following intravenous and intramuscular administration of 6.5 mg/kg in four female Friesian calves. Following single intravenous administration, the serum concentration-time curves of cefepime were best fitted using a two-compartment open model. The elimination half-life (t(1/2)beta) was 2.38+/-0.16 h, volume of distribution at steady state (Vdss) was 0.21 +/- 0.01 L/kg, and total body clearance (ClB) was 1.1 +/- 0.08 ml/min per kg. Following intramuscular administration, the drug was rapidly absorbed with an absorption half-life (t(1/2)ab) of 0.29+/-0.02 h; maximum serum concentration (Cmax) of 21.7 +/- 1.1 microg/ml was attained after (Tmax) 1.1 +/- 0.08 h; and the drug was eliminated with an elimination half-life (t(1/2)el) of 3.02 +/- 0.18 h. The systemic bioavailability (F) after intramuscular administration of cefepime in calves was 95.7% +/- 7.44%. The in vitro serum protein-binding tendency was 10.5-16.7%. Following administration by both routes, the drug was excreted in high concentrations in urine for 24 h post administration.     

Pharmacokinetics of diclofenac and its interaction with enrofloxacin in sheep

The pharmacokinetics of diclofenac was investigated in sheep given diclofenac alone (1mgkg(-1), i.v. or i.m.) and in combination with enrofloxacin (5mgkg(-1), i.v.). The plasma concentration-time data following i.v. administration of diclofenac was best described by a two compartment open pharmacokinetic model. The elimination half-life (t(1/2beta)), area under concentration-time-curve (AUC), volume of distribution (Vd(area)), mean residence time (MRT) and total body clearance (Cl(B)) were 1.03+/-0.18h, 12.17+/-1.98microg h ml(-1), 0.14+/-0.02Lkg(-1), 1.36+/-0.16h and 0.10+/-0.02Lkg(-1)h(-1), respectively. Following i.m. administration of diclofenac alone and in conjunction with enrofloxacin, the plasma concentration-time data best fitted to a one compartment open model. The t(1/2beta), AUC, Vd(area), MRT and Cl(B) were 1.33+/-0.10h, 7.32+/-1.01microg h mL(-1), 0.13+/-0.01Lkg(-1) and 0.07+/-0.01Lkg(-1)h(-1), respectively. Co-administration of enrofloxacin did not affect Vd(area) and MRT but absorption rate constant (K(a)), beta, t1/2Ka, t1/2beta, AUC, AUMC, Cl(B) and bioavailability (F) were significantly increased. This may be due to direct inhibition of cytochrome P(450) isozymes by enrofloxacin. A dose of 1.4mgkg(-1) of diclofenac administered every 6h may be appropriate for use in sheep.     

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.     

Pharmacokinetics of single doses of gentamicin given intravenously and intramuscularly to turkeys

The disposition and absorption kinetics of gentamicin were studied in healthy, mature male and female turkeys (n = 10). Single doses of gentamicin (5 mg/kg) were injected either i.v. or i.m. with a 30-day rest period between each treatment. Baseline and serial venous blood samples (n = 17) were collected from each turkey. Serum concentrations of gentamicin were determined in duplicate for 24 h after each treatment, using radio-immunoassay. Using nonlinear least-square regression methods, the combined data of the i.v. and i.m. treatments were best described by a two-compartment open model. Kinetic analysis of the data after a single i.v. dose provided the following mean values: t1/2 alpha = 0.170 +/- 0.093 h, t1/2 beta = 2.57 +/- 0.79 h, MRT = 3.62 +/- 0.96 h, Vc = 0.090 +/- 0.017 l/kg, Vd(ss) = 0.172 +/- 0.024 l/kg, Vd(area) = 0.190 +/- 0.030 l/kg, and Clt = 49.8 +/- 9.8 ml/h/kg. After a single i.m. dose, the following mean values were determined: MRT = 5.10 +/- 1.73 h, t1/2abs = 0.74 +/- 0.66 h, tlag = 0.07 +/- 0.19 h, Clt/F = 50.7 +/- 12.5 ml/h/kg, Vd(area)/F = 0.193 +/- 0.044 l/kg, and F = 102 +/- 21%. Kinetic calculations made with the single i.m. data predicted that an i.m. injection of gentamicin at the dosage rate of 3 mg/kg q. every 12 h would provide average steady state serum concentrations of 4.93 micrograms/ml.     

Pharmacokinetics and bioavailability of doxycycline in fasted and nonfasted broiler chickens

The pharmacokinetics and the influence of food on the kinetic profile and bioavailability of doxycycline was studied after a single intravenous (i.v.) and oral dose of 10.0 mg/kg body weight in 7-week-old broiler chickens. Following i.v. administration the drug was rapidly distributed in the body with a distribution half-life of 0.21 +/- 0.01 h. The elimination half-life of 6.78 +/- 0.06 h was relatively long and resulted from both a low total body clearance of 0.139 +/- 0.007 L/h.kg and a large volume of distribution of 1.36 +/- 0.06 L/kg. After oral administration to fasted chickens, the absorption of doxycycline was quite fast and substantial as shown by the absorption half-life of 0.39 +/- 0.03 h, the maximal plasma concentration of 4.47 +/- 0.16 micrograms/mL and the time to reach the Cmax of 1.73 +/- 0.06 h. The distribution and the final elimination of the drug were slower than after i.v. administration. The absolute bioavailability was 73.4 +/- 2.5%. The presence of food in the intestinal tract reduced and extended the absorption (t1/2a = 1.23 +/- 0.21 h; Cmax = 3.07 +/- 0.23 micrograms/mL; tmax = 3.34 +/- 0.21 h). The absolute bioavailability was reduced to 61.1% +/- 4.4%.     

Pharmacokinetics and metabolism of ketoprofen after intravenous and intramuscular administration in camels

The pharmacokinetics of ketoprofen were determined after an intravenous (i.v.) and intramuscular (i.m.) dose of 2.0 mg/kg body weight in five camels (Camelus dromedarius) using gas chromatography/mass spectrometry (GC/MS). The data obtained (median and range) following i.v. administration was as follows: the elimination half-life (t(1/2beta)) was 4.16 (2.65-4.29) h, the steady state volume of distribution (Vss) was 130.2 (103.4-165.3) mL/kg, volume of distribution (area method) (Vd(area)) was 321.5 (211.4-371.0) mL/kg, total body clearance (Cl) was 1.00 (0.88-1.08) mL/min x kg and renal clearance was 0.01 (0.003-0.033) mL/min x kg. Following i.m. administration, the drug was rapidly absorbed with peak serum concentration of 12.2 (4.80-14.4) microg/mL at 1.50 (1.00-2.00) h. The systemic availability of ketoprofen was complete. The apparent half-life was 3.28 (2.56-4.14) h. A hydroxylated metabolite of ketoprofen was identified by (GC/MS) under electron impact (EI) and chemical ionization (CI) scan modes. The detection times for ketoprofen and hydroxy ketoprofen in urine after an intravenous (i.v.) dose of 3.0 mg/kg body weight was 24.00 and 70.00 h, respectively. Serum protein binding of ketoprofen at 20 microg/mL was extensive; (99.1+/-0.15%).     

Toxicity, bioavailability and pharmacokinetics of a newly formulated colistin sulfate solution

We formulated a new colistin sulfate injectable solution and tested its effectiveness, toxicity and pharmacokinetics in vivo on mice, rabbits, and piglets. When intramuscularly injected (i.m.) into rabbits at 0.5 mL per site, the 2.5% colistin sulfate solution caused no reaction at the injection site, but the 5.0% solution caused the muscle circumference to appear erythematic. Tested LD50 in CD-1 mice were 38.72 mg/kg for i.m. and 431.95 mg/kg for oral administration, respectively. At 15.0 mg/kg/day (i.m.) for 5 days, colistin sulfate caused obvious neurotoxicity to piglets with moderate granular degenerations in the epithelial tissues from kidney and liver. These toxic responses were not seen when colistin sulfate was injected at 10.0 mg/kg/day for 5 days. Pharmacokinetic studies revealed Cmax of 3.73 +/- 0.28 and 6.40 +/- 0.18 microg/mL, Tmax of 32 +/- 1.5 and 34 +/- 1.8 min, t(1/2beta) of 256 +/- 14 and 264 +/- 29 min, and absolute bioavailability of 95.94 and 88.45% for colistin sulfate intramuscularly injected to piglets at 2.5 and 5.0 mg/kg, respectively. Serum colistin sulfate concentration followed a two-compartment open model showing first-order absorption. The high bioavailability and the long-lasting serum retention time indicated that the new solution is suitable for i.m. in piglets with a recommended dose of 2.5 mg/kg injected twice daily.     

A Pharmacokinetic Comparison of Meloxicam and Ketoprofen following Oral Administration to Healthy Dogs

Ketoprofen (KTP) and meloxicam (MLX) are non-steroidal anti-inflamatory drugs used extensively in veterinary medicine. The pharmacokinetics of these drugs were studied in eight dogs following a single oral dose of 1 mg/kg of KTP as a racemate or 0.2 mg/kg of MLX. The concentrations of the drugs in plasma were determined by high-performance liquid chromatography (HPLC). There were differences between the disposition curves of the KTP enantiomers, confirming that the pharmacokinetics of KTP is enantioselective. (S)-(+)-KTP was the predominant enantiomer; the S:R ratio in the plasma increased from 2.58 +/- 0.38 at 15 min to 5.72 +/- 2.35 at 1 h. The area under the concentration time curve (AUC) of (S)-(+)-KTP was approximately 6 times greater than that of (R)-(-)-KTP. The mean (+/- SD) pharmacokinetic parameters for (S)-(+)-KTP were characterized as Tmax = 0.76 +/- 0.19 h, Cmax = 2.02 +/- 0.41 microg/ml, t1/2el = 1.65 +/- 0.48 h, AUC = 6.06 +/- 1.16 microg.h/ml, Vd/F = 0.39 +/- 0.07 L/kg, Cl/F = 170 +/- 39 ml/(kg.h). The mean (+/- SD) pharmacokinetic parameters of MLX were Tmax = 8.5 +/- 1.91 h, Cmax = 0.82 +/- 0.29 microg/ml, t1/2lambda(z) = 12.13 +/- 2.15 h, AUCinf = 15.41 +/- 1.24 microg.h/ml, Vd/F = 0.23 +/- 0.03 L/ kg, and Cl/F = 10 +/- 1.4 ml/(kg.h). Our results indicate significant pharmacokinetic differences between MLX and KTP after therapeutic doses.     

Bioavailability of transdermal methimazole in a pluronic lecithin organogel (PLO) in healthy cats

The antithyroid drug methimazole is widely used for the medical management of feline hyperthyroidism. Recently, custom veterinary pharmacies have offered methimazole in a transdermal gel containing pluronic and lecithin (PLO), with anecdotal evidence of efficacy. The purpose of this study was to determine the bioavailability, relative to i.v. and oral routes of administration, of transdermal methimazole in a PLO gel in cats. Six healthy adult cats were assigned to receive 5 mg of methimazole by the i.v., oral, or transdermal routes, in a randomized triple crossover protocol with 1 week washout between doses. Blood samples were taken for high performance liquid chromatography (HPLC) determination of serum methimazole, at 0, 5, 15, 30, 60 min, and 2, 4, 6, 12 and 24 h after dosing. Methimazole absorption following transdermal administration was poor and variable, with only two of six cats achieving detectable serum methimazole concentrations at any time point following transdermal administration. Area under the concentration-time curve (AUC), maximum concentration (Cmax), and absolute bioavailability were all significantly lower for the transdermal route (0.39 +/- 0.63 microg h/mL, 0.05 +/- 0.09 microg/mL, and 11.4 +/- 18.7%, respectively) than for either i.v. (7.96 +/- 4.38 microg h/mL, 3.34 +/- 2.00 microg/mL, 100%) or oral routes (2.94 +/- 1.24 microg h/mL, 0.51 +/- 0.15 microg/mL, 40.4 +/- 8.1%). The results of this study indicate generally low to undetectable bioavailability of methimazole in a lecithin/pluronic gel given as a single transdermal dose to healthy cats, although one individual cat did achieve nearly 100% transdermal bioavailability relative to the oral route.     

The comparative plasma pharmacokinetics of intravenous cefpodoxime sodium and oral cefpodoxime proxetil in beagle dogs

The pharmacokinetic properties of cefpodoxime, and its prodrug, cefpodoxime proxetil, were evaluated in two separate studies, one following intravenous (i.v.) administration of cefpodoxime sodium and the second after oral (p.o.) administration of cefpodoxime proxetil to healthy dogs. After cefpodoxime administration, serial blood samples were collected and plasma concentrations were determined by high performance liquid chromatography (HPLC). A single i.v. administration of cefpodoxime sodium at a dose of 10 mg cefpodoxime/kg body weight resulted in a cefpodoxime average maximum plasma concentration (Cmax) of 91 (+/-17.7) microg/mL, measured at 0.5 h after drug administration, an average half-life (t1/2) of 4.67 (+/-0.680) h, an average AUC(0-infinity) of 454 (+/-83.1) h.microg/mL, an average V(d(ss)) of 151 (+/-27) mL/kg, an average Cl(B) of 22.7 (+/-4.2) mL/h/kg and an average MRT(0-infinity) of 5.97 (+/-0.573) h. When dose normalized to 10 mg cefpodoxime/kg body weight, cefpodoxime proxetil administered orally resulted in Cmax of 17.8 +/- 11.4 microg/mL for the tablet formulation and 20.1 +/- 6.20 microg/mL for the suspension formulation and an average AUC(0-LOQ) of 156 (+/-76.1) h.microg/mL for the tablet formulation and 162 (+/-48.6) h.microg/mL for the suspension formulation. Relative bioavailability of the two oral formulations was 1.04 (suspension compared with tablet), whereas the absolute bioavailability of both oral formulations was estimated to be approximately 35-36% in the cross-study comparison with the i.v. pharmacokinetics. Combined with previous studies, these results suggest that a single daily oral dose of 5-10 mg cefpodoxime/kg body weight as cefpodoxime proxetil maintains plasma concentrations effective for treatment of specified skin infections in dogs.     

Pharmacokinetics of enrofloxacin in Korean catfish (Silurus asotus)

The objective of this study was to evaluate the pharmacokinetic profile of enrofloxacin and its active metabolite, ciprofloxacin, in Korean catfish after intravenous and oral administrations. Enrofloxacin was administered to Korean catfish by a single intravenous and oral administrations at the dose of 10 mg/kg body weight. The plasma concentrations from intravenous and oral administrations of enrofloxacin were determined by LC/MS. Pharmacokinetic parameters from both routes were described to have a two-compartmental model. After intravenous and oral administrations of enrofloxacin, the elimination half-lives (t(1/2,beta)), area under the drug concentration-time curves (AUC), oral bioavailability (F) were 17.44 +/- 4.66 h and 34.13 +/- 11.50 h, 48.1 +/- 15.7 microgxh/mL and 27.3 +/- 12.4 microgxh/mL, and 64.59 +/- 4.58% respectively. The 3.44 +/- 0.81 h maximum concentration (C(max)) of 1.2 +/- 0.2 microg/mL. Ciprofloxacin, an active metabolite of enrofloxacin, was detected at all the determined time-points from 0.25 to 72 h, with the C(max) of 0.17 +/- 0.08 microg/mL for intravenous dose. After oral administration, ciprofloxacin was detected at all the time-points except 0.25 h, with the C(max) of 0.03 +/- 0.01 microg/mL at 6.67 +/- 2.31 h. Ciprofloxacin was eliminated with terminal half-life t(1/2,beta) of 52.08 +/- 17.34 h for intravenous administration and 52.43 +/- 22.37 h for oral administration.     

Pharmacokinetics of tylosin in broiler chickens

Biological availability and pharmacokinetic properties of tylosin were determined in broiler chickens after oral (p.o.) and intravenous (i.v.) administration at a dose of 10 mg/kg. The calculated bioavailability--F%, by comparing AUC values--p.o. and AUC--i.v., ranged from 30%-34%. After intravenous injection tylosin was rapidly distributed in the organism, showing elimination half-life (t1/2 beta) values of 0.52 h and distribution volume (Vd) of 0.69 L/kg, at a clearance rate (Cl) of 5.30 +/- 0.59 ml/min/kg. After oral administration, tylosin has a similar distribution volume (Vd = 0.85 L/kg), while the elimination half-life t1/2 beta of 2.07 h was four times bigger than after i.v. administration at Cl = 4.40 +/- 0.27 ml/min/kg. The obtained value tmax = 1.5 h for tylosin after oral administration indicates that using this antibiotic with drinking water in broiler chickens is the method of choice. However, a relatively low value Cmax = 1.2 micrograms/ml after oral administration of tylosin shows that dosing of this antibiotic in broiler chickens should be higher than in other food producing animals.