Distribution of penicillins into subcutaneous tissue chambers in ponies

The distribution of penicillins into a tissue chamber implanted subcutaneously in ponies was studied. Ampicillin sodium (equivalent to 15 mg/kg ampicillin) was administered intravenously. Pivampicillin, a prodrug of ampicillin, was administered by nasogastric tube to fed ponies at a dose of 19.9 mg/kg (equivalent to 15 mg/kg ampicillin). Procaine penicillin G was administered intramuscularly at a dose of 12 mg/kg (equivalent to 12 000 IU/kg). Six ponies were used for each medication. Antibiotic concentrations in plasma and tissue chamber fluid (TCF) were measured for 24 h after administration. Mean peak concentrations of ampicillin in TCF were 7.3 μg/mL, reached at 1.7 h, and 1.3 μg/mL, reached at 2.7 h, after administration of ampicillin sodium and pivampicillin respectively. The mean peak concentration of penicillin G of 0.3 μg/mL was reached 12.3 h after administration of procaine penicillin G. Concentrations in TCF remained above the minimum inhibitory concentration of Streptococcus zooepidemicus for the proposed dosing intervals of 8, 12 and 24 h for ampicillin sodium, pivampicillin and procaine penicillin G respectively.     

Pharmacokinetic/pharmacodynamic relationship of cefquinome against Pasteurella multocida in a tissue‐cage model in yellow cattle

The cephalosporin antimicrobial drug cefquinome was administered to yellow cattle intravenously (i.v.) and intramuscularly (i.m.) at a dose of 1 mg/kg of body weight in a two‐period crossover study. The pharmacokinetic (PK) properties of cefquinome in serum, inflamed tissue‐cage fluid (exudate), and noninflamed tissue‐cage fluid (transudate) were studied using a tissue‐cage model. The in vitro and ex vivo activities of cefquinome in serum, exudate, and transudate against a pathogenic strain of Pasteurella multocida (P. multocida) were determined. A concentration‐independent antimicrobial activity of cefquinome was confirmed for levels lower than 4 × MIC. Integration of in vivo pharmacokinetic data with the in vitro MIC provided mean values for the time that drug levels remain above the MIC (T > MIC) in serum was 14.10 h after intravenous and 14.46 h after intramuscular dosing, indicating a likely high level of effectiveness in clinical infections caused by P. multocida of MIC 0.04 μg/mL or less. These data may be used as a rational basis for setting dosing schedules, which optimize clinical efficacy and minimize the opportunities for emergence of resistant organisms.     

Pharmacokinetics of tildipirosin in bovine plasma,lung tissue,and bronchial fluid (from live,nonanesthetized cattle)

Menge, M., Rose, M., Bohland, C., Zschiesche, E., Kilp, S., Metz, W., Allan, M., Röpke, R., Nürnberger, M. Pharmacokinetics of tildipirosin in bovine plasma, lung tissue, and bronchial fluid (from live, nonanesthetized cattle). J. vet. Pharmacol. Therap.  35 , 550–559. The pharmacokinetics of tildipirosin (Zuprevo^® 180 mg/mL solution for injection for cattle), a novel 16‐membered macrolide for treatment, control, and prevention of bovine respiratory disease, were investigated in studies collecting blood plasma, lung tissue, and in vivo samples of bronchial fluid (BF) from cattle. After single subcutaneous (s.c.) injection at 4 mg/kg body weight, maximum plasma concentration (C_max) was 0.7 μg/mL. T_max was 23 min. Mean residence time from the time of dosing to the time of last measurable concentration (MRT_last) and terminal half‐life (T_1/2) was 6 and 9 days, respectively. A strong dose–response relationship with no significant sex effect was shown for both C_max and area under the plasma concentration–time curve from time 0 to the last sampling time with a quantifiable drug concentration (AUC_last) over the range of doses up to 6 mg/kg. Absolute bioavailability was 78.9%. The volume of distribution based on the terminal phase (V_z) was 49.4 L/kg, and the plasma clearance was 144 mL/h/kg. The time–concentration profile of tildipirosin in BF and lung far exceeded those in blood plasma. In lung, tildipirosin concentrations reached 9.2 μg/g at 4 h, peaked at 14.8 μg/g at day 1, and slowly declined to 2.0 μg/g at day 28. In BF, the concentration of tildipirosin reached 1.5 and 3.0 μg/g at 4 and 10 h, maintained a plateau of about 3.5 μg/g between day 1 and 3, and slowly declined to 1.0 at day 21. T_1/2 in lung and BF was approximately 10 and 11 days. Tildipirosin is rapidly and extensively distributed to the respiratory tract followed by slow elimination.     

Identification of flunixin glucuronide and depletion of flunixin and its marker residue in bovine milk

Residues of flunixin [and its marker residue 5‐hydroxyflunixin (5OHFLU)] were determined in milk from cows that intravenously received therapeutic doses of the drug. The samples were collected during each milking (every 12 h) for six consecutive days, and concentrations of flunixin and its metabolites were determined by the method with and without enzymatic hydrolysis (beta‐glucuronidase). The highest flunixin concentration in milk was observed 12 h after dosing (2.4 ± 1.42 μg/kg, mean ± SD). Flunixin concentrations in the samples determined with enzymatic hydrolysis were significantly higher (P < 0.05), which suggests the transfer of flunixin glucuronide to the milk. Additionally, unambiguous identification of flunixin glucuronide in the bovine milk was performed with linear ion‐trap mass spectrometry. The 5OHFLU concentrations analyzed without enzymatic hydrolysis (22.3 ± 16.04 μg/kg) were similar to this obtained with enzymatic hydrolysis. Flunixin and 5OHFLU concentrations dropped below the limits of detection at 48 h after last dosing.     

Pharmacokinetics of tobramycin following intravenous,intramuscular, and intra‐articular administration in healthy horses

The objectives of this study were to examine the pharmacokinetics of tobramycin in the horse following intravenous (IV), intramuscular (IM), and intra‐articular (IA) administration. Six mares received 4 mg/kg tobramycin IV, IM, and IV with concurrent IA administration (IV+IA) in a randomized 3‐way crossover design. A washout period of at least 7 days was allotted between experiments. After IV administration, the volume of distribution, clearance, and half‐life were 0.18 ± 0.04 L/kg, 1.18 ± 0.32 mL·kg/min, and 4.61 ± 1.10 h, respectively. Concurrent IA administration could not be demonstrated to influence IV pharmacokinetics. The mean maximum plasma concentration (C_max) after IM administration was 18.24 ± 9.23 μg/mL at 1.0 h (range 1.0–2.0 h), with a mean bioavailability of 81.22 ± 44.05%. Intramuscular administration was well tolerated, despite the high volume of drug administered (50 mL per 500 kg horse). Trough concentrations at 24 h were below 2 μg/mL in all horses after all routes of administration. Specifically, trough concentrations at 24 h were 0.04 ± 0.01 μg/mL for the IV route, 0.04 ± 0.02 μg/mL for the IV/IA route, and 0.02 ± 0.02 for the IM route. An additional six mares received IA administration of 240 mg tobramycin. Synovial fluid concentrations were 3056.47 ± 1310.89 μg/mL at 30 min after administration, and they persisted for up to 48 h with concentrations of 14.80 ± 7.47 μg/mL. Tobramycin IA resulted in a mild chemical synovitis as evidenced by an increase in synovial fluid cell count and total protein, but appeared to be safe for administration. Monte Carlo simulations suggest that tobramycin would be effective against bacteria with a minimum inhibitory concentration (MIC) of 2 μg/mL for IV administration and 1 μg/mL for IM administration based on C_max:MIC of 10.     

Effect of sucralfate on oral minocycline absorption in healthy dogs

Sucralfate and minocycline may be administered concurrently to dogs. The relative bioavailability of tetracyclines may be reduced if administered with sucralfate, but studies confirming these interactions in dogs are not available. This study evaluated the pharmacokinetics of oral minocycline in dogs (M), determined the effects of concurrent administration of sucralfate and minocycline (MS) on minocycline pharmacokinetics, determined the effects of delaying sucralfate administration by 2 h (MS+2) on minocycline pharmacokinetics, and established dosing recommendations based on pharmacodynamic indices. Oral minocycline (300 mg) and sucralfate suspension (1 g) were administered to five greyhounds in a randomized crossover design. Minocycline plasma concentrations were evaluated using liquid chromatography with mass spectrometry. The maximum plasma concentration (C_MAX) and area under the curve (AUC) of minocycline were 1.15 μg/mL and 8.0 h* μg/mL, respectively. The C_MAX and AUC were significantly lower (P < 0.05) in the MS group (C_MAX = 0.33 μg/mL, AUC 3.0 h*μg/mL) compared with M or MS+2 (C_MAX = 0.97 μg/mL, AUC 10.3 h*μg/mL). Delaying sucralfate by 2 h did not decrease oral minocycline absorption, but concurrent administration significantly decreased minocycline absorption. A dose of 7.5 mg/kg p.o. q12 h achieves the pharmacodynamic index for a bacterial minimum inhibitory concentration (MIC) of 0.25 μg/mL (AUC:MIC≥33.9).     

Pharmacokinetics of amoxicillin trihydrate in cultured olive flounder (Paralichthys olivaceus)

The study was aimed at investigating the pharmacokinetics of amoxicillin trihydrate (AMOX) in olive flounder (Paralichthys olivaceus) following oral, intramuscular, and intravenous administration, using high‐performance liquid chromatography following. The maximum plasma concentration (C_max), following oral administration of 40 and 80 mg/kg body weight (b.w.), AMOX was 1.14 (T_max, 1.7 h) and 0.76 μg/mL (T_max, 1.6 h), respectively. Intramuscular administration of 30 and 60 mg/kg of AMOX resulted in C_max values of 4 and 4.3 μg/mL, respectively, with the corresponding T_max values of 29 and 38 h. Intravenous administration of 6 mg/kg AMOX resulted in a C_max of 9 μg/mL 2 h after administration. Following oral administration of 40 and 80 mg/kg AMOX, area under the curve (AUC) values were 52.257 and 41.219 μg/mL·h, respectively. Intramuscular 30 and 60 mg/kg doses resulted in AUC values of 370.274 and 453.655 μg/mL·h, respectively, while the AUC following intravenous administration was 86.274 μg/mL·h. AMOX bioavailability was calculated to be 9% and 3.6% following oral administration of 40 and 80 mg/kg, respectively, and the corresponding values following intramuscular administration were 86% and 53%. In conclusion, this study demonstrated high bioavailability of AMOX following oral administration in olive flounder.     

Alternate‐day dosing of itraconazole in healthy adult cats

The current available formulations of itraconazole are not ideal for dosing in cats. The capsular preparation often does not allow for accurate dosing, the oral solution is difficult to administer and poorly tolerated, and the bioavailability of compounded formulations has been shown to be poor in other species. The aim of this study was to evaluate every other day dosing of 100 mg itraconazole capsule in healthy adult cats. Ten healthy adult cats received a 100 mg capsule of itraconazole orally every 48 h for 8 weeks. Peak and trough serum concentrations of itraconazole were measured weekly using high‐performance liquid chromatography (HPLC). Physical examination, complete blood count (CBC), and chemistry profiles were performed weekly. The dosage regimen achieved average therapeutic trough concentrations (>0.5 μg/mL) within 3 weeks. The protocol yielded no adverse effects in 8 of the 10 study cats, with affected cats recovering fully with discontinuation of the drug and supportive care. At 8 weeks, an average peak concentration of 1.79 ± 0.952 μg/mL (95% CI: 0.996–2.588) and an average trough concentration of 0.761 ± 0.540 μg/mL (95% CI: 0.314–1.216) were achieved. Overall, a 100 mg every other day oral dosage regimen for itraconazole in cats yielded serum concentrations with minimal fluctuation and with careful monitoring may be considered for treatment of cats with systemic fungal disease.     

Pharmacokinetics of amoxicillin trihydrate in male Asian elephants (Elephas maximus) following intramuscular administration

The purpose of this study was to investigate the pharmacokinetic characteristics of amoxicillin (AMX) trihydrate in male Asian elephants, Elephas maximus, following intramuscular administration at two dosages of 5.5 and 11 mg/kg body weight (b.w.). Blood samples were collected from 0.5 up to 72 h. The concentration of AMX in elephant plasma was measured using liquid chromatography electrospray ionization mass spectrometry. AMX was measurable up to 24 h after administration at two dosages. Peak plasma concentration (C_max) was 1.20 ± 0.39 μg/mL after i.m. administration at a dosage of 5.5 mg/kg b.w., whereas it was 3.40 ± 0.63 μg/mL at a dosage of 11 mg/kg b.w. A noncompartment model was developed to describe the disposition of AMX in Asian elephants. Based on the preliminary findings found in this research, the dosage of 5.5 and 11 mg/kg b.w. produced drug plasma concentrations higher than 0.25 mg/mL for 24 h after i.m. administration. Thereafter, i.m. administration with AMX at a dosage of 5.5 mg/kg b.w. appeared a more suitable dose than 11 mg/kg b.w. However, more studies are needed to determine AMX clinical effectiveness in elephants.     

Plasma and synovial fluid pharmacokinetics of cefquinome following the administration of multiple doses in horses

The plasma and synovial fluid pharmacokinetics and safety of cefquinome, a 2‐amino‐5‐thiazolyl cephalosporin, were determined after multiple intravenous administrations in sixteen healthy horses. Cefquinome was administered to each horse through a slow i.v. injection over 20 min at 1, 2, 4, and 6 mg/kg (n = 4 horses per dose) every 12 h for 7 days (a total of 13 injections). Serial blood and synovial fluid samples were collected during the 12 h after the administration of the first and last doses and were analyzed by a high‐performance liquid chromatography assay. The data were evaluated using noncompartmental pharmacokinetic analyses. The estimated plasma pharmacokinetic parameters were compared with the hypothetical minimum inhibitory concentration (MIC) values (0.125–2 μg/mL). The plasma and synovial fluid concentrations and area under the concentration–time curves (AUC) of cefquinome showed a dose‐dependent increase. After a first dose of cefquinome, the ranges for the mean plasma half‐life values (2.30–2.41 h), the mean residence time (1.77–2.25 h), the systemic clearance (158–241 mL/h/kg), and the volume of distribution at steady‐state (355–431 mL/kg) were consistent across dose levels and similar to those observed after multiple doses. Cefquinome did not accumulate after multiple doses. Cefquinome penetrated the synovial fluid with AUC_{synovial fluid}/AUC_plasma ratios ranging from 0.57 to 1.37 after first and thirteenth doses, respectively. Cefquinome is well tolerated, with no adverse effects. The percentage of time for which the plasma concentrations were above the MIC was >45% for bacteria, with MIC values of ≤0.25, ≤0.5, and ≤1 μg/mL after the administration of 1, 2, and 4 or 6 mg/kg doses of CFQ at 12‐h intervals, respectively. Further studies are needed to determine the optimal dosage regimes in critically ill patients.     

Elevation and prolongation of serum ampicillin and amoxycillin concentrations in calves by the concomitant administration of probenecid

The effects of probenecid on serum ampicillin and amoxycillin concentrations were investigated in 1–5 week old calves after oral and parenteral drug administration. Ampicillin trihydrate was administered orally at 250mg/calf, after an overnight fast, alone and with 1.5g probenecid. Peak serum ampicillin concentrations were elevated from 0.60 to 1.22 μg/ml by the co-administration of probenecid. In calves given 0.5 g amoxycillin trihydrate with the milk replacer, peak serum drug concentration increased from 1.74 to 3.16 μg/ml when 1.5 g probenecid was given too. Maximal effect of probenecid administered orally was with the 1.5 g/calf dose with considerably lesser increase in peak serum amoxycillin being observed with doses of 0.5 g, 1 g and 2 g/calf. After parenteral injection of probenecid solution at 1 g and 2 g/calf serum ampicillin concentrations peaked at more than twice the concentrations measured after equal doses of the two antibiotics were injected alone. The co-administration of 2 g probenecid and 1 g sodium ampicillin or 0.5 g sodium amoxycillin parenterally resulted in peak antibiotic concentrations considered to be effective against some of the more resistant pathogenic Gram-negative bacteria associated with diseases in calves and serum antibiotic concentrations 5 μg/ml were maintained during 5–6 h as opposed to 2–3 h after the antibiotics were injected alone. Oral administration of 1.5 g probenecid at three consecutive milk feeding times did not alter serum urea or serum creatinine concentrations.     

Some pharmacokinetic indices of oral fluconazole administration to koalas (Phascolarctos cinereus) infected with cryptococcosis

Three asymptomatic koalas serologically positive for cryptococcosis and two symptomatic koalas were treated with 10 mg/kg fluconazole orally, twice daily for at least 2 weeks. The median plasma C_max and AUC_0‐8 h for asymptomatic animals were 0.9 μg/mL and 4.9 μg/mL·h, respectively; and for symptomatic animals 3.2 μg/mL and 17.3 μg/mL·h, respectively. An additional symptomatic koala was treated with fluconazole (10 mg/kg twice daily) and a subcutaneous amphotericin B infusion twice weekly. After 2 weeks the fluconazole C_max was 3.7 μg/mL and the AUC_0‐8 h was 25.8 μg/mL*h. An additional three koalas were treated with fluconazole 15 mg/kg twice daily for at least 2 weeks, with the same subcutaneous amphotericin protocol co‐administered to two of these koalas (C_max: 5.0 μg/mL; mean AUC_0‐8 h: 18.1 μg/mL*h). For all koalas, the fluconazole plasma C_max failed to reach the MIC₉₀ (16 μg/mL) to inhibit C. gattii. Fluconazole administered orally at either 10 or 15 mg/kg twice daily in conjunction with amphotericin is unlikely to attain therapeutic plasma concentrations. Suggestions to improve treatment of systemic cryptococcosis include testing pathogen susceptibility to fluconazole, monitoring plasma fluconazole concentrations, and administration of 20–25 mg/kg fluconazole orally, twice daily, with an amphotericin subcutaneous infusion twice weekly.     

Pharmacokinetics of danofloxacin and N‐desmethyldanofloxacin in adult horses and their concentration in synovial fluid

The objectives of this study were to investigate the pharmacokinetics of danofloxacin and its metabolite N‐desmethyldanofloxacin and to determine their concentrations in synovial fluid after administration by the intravenous, intramuscular or intragastric routes. Six adult mares received danofloxacin mesylate administered intravenously (i.v.) or intramuscularly (i.m.) at a dose of 5 mg/kg, or intragastrically (IG) at a dose of 7.5 mg/kg using a randomized Latin square design. Concentrations of danofloxacin and N‐desmethyldanofloxacin were measured by UPLC‐MS/MS. After i.v. administration, danofloxacin had an apparent volume of distribution (mean ± SD) of 3.57 ± 0.26 L/kg, a systemic clearance of 357.6 ± 61.0 mL/h/kg, and an elimination half‐life of 8.00 ± 0.48 h. Maximum plasma concentration (C_max) of N‐desmethyldanofloxacin (0.151 ± 0.038 μg/mL) was achieved within 5 min of i.v. administration. Peak danofloxacin concentrations were significantly higher after i.m. (1.37 ± 0.13 μg/mL) than after IG administration (0.99 ± 0.1 μg/mL). Bioavailability was significantly higher after i.m. (100.0 ± 12.5%) than after IG (35.8 ± 8.5%) administration. Concentrations of danofloxacin in synovial fluid samples collected 1.5 h after administration were significantly higher after i.v. (1.02 ± 0.50 μg/mL) and i.m. (0.70 ± 0.35 μg/mL) than after IG (0.20 ± 0.12 μg/mL) administration. Monte Carlo simulations indicated that danofloxacin would be predicted to be effective against bacteria with a minimum inhibitory concentration (MIC) ≤0.25 μg/mL for i.v. and i.m. administration and 0.12 μg/mL for oral administration to maintain an area under the curve:MIC ratio ≥50.     

A microbiological assay to estimate the antimicrobial activity of parenteral tildipirosin against foodborne pathogens and commensals in the colon of beef cattle and pigs

Tildipirosin (TIP) is a novel 16‐membered‐ring macrolide authorized for the treatment of bovine and swine respiratory disease. The pH dependency of macrolide antimicrobial activity is well known. Considering that the pH in the colon contents of growing beef cattle and pigs is usually below pH 7.0, the minimum inhibitory concentrations (MIC) of TIP against foodborne bacterial pathogens such as Campylobacter (C.) coli, C. jejuni and Salmonella enterica and commensal species including Enterococcus (E.) faecalis, E. faecium and Escherichia coli were determined under standard (pH 7.3 ± 1) or neutral as well as slightly acidic conditions. A decrease in pH from 7.3 to 6.7 resulted in an increase in MICs of TIP. Except for the MICs > 256 μg/mL observed in the resistant subpopulation of the C. coli and the Enterococcus species, the MIC ranges increased from 2–8 μg/mL to 64–> 256 μg/mL for Salmonella enterica and E. coli, from 8–16 μg/mL to 32–128 μg/mL for the two Campylobacter species, and from 4–32 μg/mL to 128–> 256 μg/mL for both Enterococcus species. To estimate the antimicrobial activity of TIP in the colon contents of livestock during recommended usage of the parenterally administered TIP (Zuprevo^®), and to compare this with the increased MICs at the slightly acidic colonic pH, we developed and validated a microbiological assay for TIP and used this to test incurred faecal samples collected from cattle and pigs. Microbiological activity of luminal TIP was determined in aqueous supernatants from diluted faeces, using standard curves produced from TIP‐spiked faecal supernatants. The limit of quantification (LOQ) for TIP was 1 μg/mL (ppm). In a cattle study (n = 14), 3 of 28 faecal samples collected 24 and 48 h post‐treatment were found to contain TIP above the LOQ (concentrations of 1.3–1.8 ppm). In another cattle study (n = 12) with faecal samples collected at 8, 24 and 48 h post‐treatment, TIP concentrations were above the LOQ in 4 of the 8 h samples (1.2–2.6 ppm) and one of the 24‐h samples (1.3 ppm). In a pig study (n = 12) with faecal samples collected 24, 48 and 72 h post‐treatment, only one sample contained TIP above the LOQ (concentration 1.5 ppm). In another pig study (n = 12), with samples collected at 8, 24 48 and 96 h post‐treatment, TIP concentrations were above the LOQ in one 8‐h sample (1.1 ppm) and two 24‐h samples (2.3 and 2.5 ppm). None of the 48‐h and 96‐h samples from these 4 studies contained measurable TIP concentrations. Thus, in cattle and pigs, only a small fraction of faecal samples collected up to 24 h postdosing contained measurable microbiologically active TIP, with its maximum limited to 2.6 μg/mL. This is several log₂ dilution steps below the MICs of TIP against foodborne pathogens and commensals collected under acidic conditions comparable with those in the colonic contents and may explain a lack of intestinal dysbacteriosis with parenteral tildipirosin in livestock.     

Pharmacokinetic evaluation of oral dantrolene in the dog

The pharmacokinetics of dantrolene and its active metabolite, 5‐hydroxydantrolene, after a single oral dose of either 5 or 10 mg/kg of dantrolene was determined. The effects of exposure to dantrolene and 5‐hydroxydantrolene on activated whole‐blood gene expression of the cytokines interleukin‐2 (IL‐2) and interferon‐γ (IFN‐γ) were also investigated. When dantrolene was administered at a 5 mg/kg dose, peak plasma concentration (C_max) was 0.43 μg/mL, terminal half‐life (t_1/2) was 1.26 h, and area under the time–concentration curve (AUC) was 3.87 μg·h/mL. For the 10 mg/kg dose, C_max was 0.65 μg/mL, t_1/2 was 1.21 h, and AUC was 5.94 μg·h/mL. For all calculated parameters, however, there were large standard deviations and wide ranges noted between and within individual dogs: t_1/2, for example, ranged from 0.43 to 6.93 h, C_max ratios ranged from 1.05 to 3.39, and relative bioavailability (rF) values ranged from 0.02 to 1.56. While activated whole‐blood expression of IL‐2 and IFN‐γ as measured by qRT‐PCR was markedly suppressed following exposure to very high concentrations (30 and 50 μg/mL, respectively) of both dantrolene and 5‐hydroxydantrolene, biologically and therapeutically relevant suppression of cytokine expression did not occur at the much lower drug concentrations achieved with oral dantrolene dosing.     

Pharmacokinetic study of enrofloxacin in Nile tilapia (Oreochromis niloticus) after a single oral administration in medicated feed

The objective of this study was to evaluate the disposition kinetics of enrofloxacin (ENR) in the plasma and its distribution in the muscle tissue of Nile tilapia (Oreochromis niloticus) after a single oral dose of 10 mg/kg body weight via medicated feed. The fish were kept at a temperature between 28 and 30 °C. The collection period was between 30 min and 120 h after administration of the drug. The samples were analyzed by high‐performance liquid chromatography with a fluorescence detector (HPLC‐FLD). The ENR was slowly absorbed and eliminated from the plasma (C_max = 1.24 ± 0.37 μg/mL; T_max = 8 h; T_1/2Ke = 19.36 h). ENR was efficiently distributed in the muscle tissue and reached maximum values (2.17 ± 0.74 μg/g) after 8 h. Its metabolite, ciprofloxacin (CIP), was detected and quantified in the plasma (0.004 ± 0.005 μg/mL) and muscle (0.01 ± 0.011 μg/g) for up to 48 h. After oral administration, the mean concentration of ENR in the plasma was well above the minimum inhibitory concentrations (MIC₅₀) for most bacteria already isolated from fish except for Streptococcus spp. This way the dose used in this study allowed for concentrations in the blood to treat the diseases of tilapia.     

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 metronidazole in foals: influence of age within the neonatal period

Neonatal foals have unique pharmacokinetics, which may lead to accumulation of certain drugs when adult horse dosage regimens are used. Given its lipophilic nature and requirement for hepatic metabolism, metronidazole may be one of these drugs. The purpose of this study was to determine the pharmacokinetic profiles of metronidazole in twelve healthy foals at 1–2.5 days of age when administered as a single intravenous (IV) and intragastric (IG) dose of 15 mg/kg. Foals in the intravenous group were studied a second time at 10–12 days of age to evaluate the influence of age on pharmacokinetics within the neonatal period. Blood samples were collected at serial time points after metronidazole administration. Metronidazole concentration in plasma was measured using LC‐MS. Pharmacokinetic parameters were determined using noncompartmental analysis and compared between age groups. At 1–2.5 days of age, the mean peak plasma concentration after IV infusion was 18.79 ± 1.46 μg/mL, elimination half‐life was 11.8 ± 1.77 h, clearance was 0.84 ± 0.13 mL/min/kg and the volume of distribution (steady‐state) was 0.87 ± 0.07 L/kg. At 10–12 days of age, the mean peak plasma concentration after IV infusion was 18.17 ± 1.42 μg/mL, elimination half‐life was 9.07 ± 2.84 h, clearance was 1.14 ± 0.21 mL/min/kg and the volume of distribution (steady‐state) was 0.88 ± 0.06 L/kg. Oral approximated bioavailability was 100%. Cmax and T_max after oral dosing were 14.85 ± 0.54 μg/mL and 1.75 (1–4) h, respectively. The elimination half‐life was longer and clearance was reduced in neonatal foals at 1–2.5 days as compared to 10–12 days of age (P = 0.006, P = 0.001, respectively). This study warrants consideration for altered dosing recommendations in foals, especially a longer interval (12 h).     

Comparative pharmacokinetics of ampicillin trihydrate, gentamicin sulphate and oxytetracycline hydrochloride in Nubian goats and desert sheep

In this investigation the pharmacokinetics of three commonly used antibiotics, ampicillin trihydrate (10 mg/kg), gentamicin sulphate (3 mg/kg) and oxytetracycline hydrochloride (5 mg/kg), given intravenously, were each studied in five Nubian goats and five desert sheep. The pharmacokinetic parameters were described by a two-compartment open model. The results indicated that there were significant differences between the two species in some kinetic parameters of ampicillin and oxytetracycline but not gentamicin. Ampicillin elimination half life ( t _1/2β) in goats (1.20 h) was shorter than that in sheep (2.48 h), and its clearance ( Cl ) significantly higher in goats (2921mL/h·kg) compared to sheep (262 mL/h·kg) ( P < 0.01). Ampicillin volume of distribution ( V d_area) was found to be significantly larger in goats (5673 mL/kg) than in sheep (992 mL/kg) ( P < 0.01). For oxytetracycline, the t _1/2β in goats (3.89 h) was significantly shorter than that in sheep (6.30 h) and the Cl value in goats (437 mL/h·kg) was significantly higher than in sheep (281 mL/h·kg). The results suggest that when treating sheep and goats, the pharmacokinetic differences between the two species must be considered in order to optimize the therapeutic doses of ampicillin and oxytetracycline.