The pharmacokinetics of pimobendan enantiomers after oral and intravenous administration of racemate pimobendan formulations in healthy dogs

Pimobendan is a benzimidazole‐pyridazinone derivative, marketed as a racemic mixture for the management of canine heart failure. Pharmacokinetics of the enantiomers of pimobendan and its oral bioavailability have not been described in dogs. The aim of this study was to describe pharmacokinetics of three formulations of pimobendan in healthy dogs: the licensed capsule product, and novel liquid and intravenous formulations. A three‐period, nested randomized two‐treatment crossover design was used. Pimobendan was administered p.o. at 0.25 and i.v. at 0.125 mg/kg. Blood and plasma samples were analysed by liquid chromatography–mass spectrometry. Noncompartmental modelling was used to describe the pharmacokinetics. Parameters were compared between formulations using a general linear model. Bioequivalence of the oral formulations was tested using CI90 for AUC_(0–∞) and C_max. Bioavailability of pimobendan after oral dosing was 70%. Liquid and capsule formulations were bioequivalent only for AUC. The positive enantiomer of pimobendan (PE) had a larger volume of distribution than the negative enantiomer (NE) (281 ± 48 vs. 215 ± 68 mL/kg; P = 0.003) and a shorter half‐life (21.7 vs. 29.9 min; P = 0.004). The NE was distributed more quickly than the PE into blood cells. Enantiomers of pimobendan have differing absorption, distribution and elimination. The pharmacokinetics of pimobendan in healthy dogs was described.     

Oral,subcutaneous, and intravenous pharmacokinetics of ondansetron in healthy cats

Ondansetron is a 5‐HT₃ receptor antagonist that is an effective anti‐emetic in cats. The purpose of this study was to evaluate the pharmacokinetics of ondansetron in healthy cats. Six cats with normal complete blood count, serum biochemistry, and urinalysis received 2 mg oral (mean 0.43 mg/kg), subcutaneous (mean 0.4 mg/kg), and intravenous (mean 0.4 mg/kg) ondansetron in a cross‐over manner with a 5‐day wash out. Serum was collected prior to, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18, and 24 h after administration of ondansetron. Ondansetron concentrations were measured using liquid chromatography coupled to tandem mass spectrometry. Noncompartmental pharmacokinetic modeling and dose interval modeling were performed. Repeated measures anova was used to compare parameters between administration routes. Bioavailability of ondansetron was 32% (oral) and 75% (subcutaneous). Calculated elimination half‐life of ondansetron was 1.84 ± 0.58 h (intravenous), 1.18 ± 0.27 h (oral) and 3.17 ± 0.53 h (subcutaneous). The calculated elimination half‐life of subcutaneous ondansetron was significantly longer (P < 0.05) than oral or intravenous administration. Subcutaneous administration of ondansetron to healthy cats is more bioavailable and results in a more prolonged exposure than oral administration. This information will aid management of emesis in feline patients.     

Use of pimobendan in 170 cats (2006–2010)

Hypothesis/ObjectivesTo describe the therapeutic use of pimobendan in cats, describe the patient population to which it was administered, document potential side effects and report the clinical course following administration of pimobendan in conjunction with standard heart failure therapy. It is hypothesized that cats with advanced heart disease including congestive heart failure from a variety of causes will tolerate pimobendan with a minimum of side effects when used in treatment in conjunction with a variety of other medications.Animals, materials and methodsOne hundred and seventy client owned cats with naturally occurring heart disease, one hundred and sixty four of which had congestive heart failure. Medical records were reviewed and owners and referring veterinarians were contacted for follow-up data. Data collected included pimobendan dose, other medications administered concurrently, data collected at physical examination, presence or absence of heart failure, adverse effects, classification of heart disease, echocardiographic data and survival time. The data were analyzed for significance between the initial visit and any follow-up visits.ResultsAll cats were treated with pimobendan. The median pimobendan dose was 0.24 mg/kg q 12 h. Pimobendan was used in combination with multiple concurrent medications including angiotensin converting enzyme inhibitors, diuretics and anti-thrombotics. Five cats (3.0%) had potential side effects associated with pimobendan. One cat (0.6%) had presumed side effects severe enough to discontinue pimobendan use. Median survival time for 164 cats with congestive heart failure after initiation of pimobendan was 151 days (range 1–870).ConclusionPimobendan appears to be well tolerated in cats with advanced heart disease when used with a variety of concurrent medications. Randomized controlled studies need to be performed to accurately assess whether it is efficacious for treatment of congestive heart failure in cats.     

A pharmacokinetic and residual study of sulfadiazine/trimethoprim in mandarin fish (Siniperca chuatsi) with single‐ and multiple‐dose oral administrations

A pharmacokinetic and tissue residue study of sulfadiazine combined with trimethoprim (SDZ/TMP = 5/1) was conducted in Siniperca chuatsi after single‐ (120 mg/kg) or multiple‐dose (an initial dose of 120 mg/kg followed by a 5‐day consecutive dose of 60 mg/kg) oral administrations at 28 °C. The absorption half‐life (t_1/2α), elimination half‐life (t_1/2β), volume of distribution (V_d/F), and the total body clearance (Cl_B/F) for SDZ and TMP were 4.3 ± 1.7 to 6.3 ± 1.8 h and 2.4 ± 1.0 to 3.9 ± 0.9 h, 25.9 ± 4.5 to 53.0 ± 5.6 h and 11.8 ± 3.5 to 17.1 ± 3.4 h, 2.34 ± 0.78 to 3.67 ± 0.99 L/kg and 0.39 ± 0.01 to 1.33 ± 0.57 L/kg, and 0.03 ± 0.01 to 0.06 ± 0.01 L/kg·h and 0.02 ± 0.01 to 0.05 ± 0.01 L/kg·h, respectively, after the single dose. The elimination half‐life (t_1/2β) and mean residue time (MRT) for SDZ and TMP were 68.8 ± 7.8 to 139.8 ± 12.3 h and 34.0 ± 5.5 to 56.1 ± 6.8 h, and 99.3 ± 6.1 to 201.7 ± 11.5 h and 49.1 ± 3.5 to 81.0 ± 5.1 h, respectively, after the multiple‐dose administration. The daily oral SDZ/TMP administration might cause a high tissue concentration and long t_1/2β, thereby affecting antibacterial activity. The withdrawal time for this oral SDZ/TMP formulation (according to the accepted guidelines in Europe for maximum residue limits, <0.1 mg/kg of tissues for sulfonamides, and <0.05 mg/kg for TMP) should not be <36 days for fish.     

Pharmacokinetics of amoxicillin/clavulanic acid combination after intravenous and oral administration in goats

Summary

The intravenous and oral pharmacokinetics of an amoxicillin and clavulanic acid combination (20 mg/kg of sodium amoxicillin and 5 mg/kg of potassium clavulanate) were studied in six goats. After intravenous administration the pharmacokinetics of both drugs could be described by an open two‐compartment model. Amoxicillin had a greater distribution volume (0.19 ± 0.01 l/kg) than clavulanic acid (0.15 ± 0.01 l/kg), whereas the distribution and elimination constants were higher for the latter, which was eliminated more quickly than amoxicillin. After oral administration of both drugs their pharmacokinetic behaviour was best described by an open one‐compartment model with first‐order absorption. Elimination half‐lives were twice as long after oral (2.15 ± 0.20 h and 1.94 ± 0.16 h for amoxicillin and clavulanic acid respectively) than after intravenous administration (1.20 ± 0.16 h and 0.86 ± 0.09, respectively). An apparent ‘flip‐flop’ situation was evident in this study. Bioavailability was 27% for amoxicillin and 50% for clavulanic acid.     

Lung microdialysis study of florfenicol in pigs after single intramuscular administration

For most bacterial lung infections, the concentration of unbound antimicrobial agent in lung interstitial fluid has been considered as the gold standard for estimating the antibacterial efficacy. In this study, the pharmacokinetics of florfenicol (FF) in porcine lung interstitial fluid was investigated after single intramuscular administration at two different doses (20 and 50 mg/kg). Twelve pigs underwent thoracotomy under general anesthesia. Then, the CMA/30 probe was implanted into the lung and perfused at 1 μL/min. The microdialysis (MD) samples were collected on a preset schedule and analyzed by high‐performance liquid chromatography (HPLC). Noncompartmental pharmacokinetic analysis was performed. FF exhibited rapid distribution and slow elimination in porcine lung interstitial fluid. The main pharmacokinetic parameters at 20 and 50 mg/kg were 4.88 ± 0.54 and 10.36 ± 2.52 μg/mL for the maximum concentration (C_max), 3.25 ± 0.32 and 3.50 ± 0.27 h for the time to C_max (T_max), 9.47 ± 6.84 and 7.75 ± 3.23 h for the half‐life (t_1/2), 0.10 ± 0.06 and 0.10 ± 0.04 1/h for the terminal elimination rate constant (λ_z), 13.85 ± 7.97 and 11.42 ± 2.79 h for the mean residence time (MRT), 37.77 ± 8.13 and 71.15 ± 16.99 h·μg/mL for the area under the curve from time 0 to 18.25 h (AUC_0–18.25), and 51.18 ± 20.11 and 88.78 ± 27.58 h·μg/mL for the area under the curve from time 0 to infinity (AUC_0–∞), respectively.     

Pharmacokinetics and cardiovascular effects following a single oral administration of a nonaqueous pimobendan solution in healthy dogs

Pimobendan is an inodilator used in the treatment of canine congestive heart failure (CHF). The aim of this study was to investigate the pharmacokinetics and cardiovascular effects of a nonaqueous oral solution of pimobendan using a single‐dose, operator‐blinded, parallel‐dose study design. Eight healthy dogs were divided into two treatment groups consisting of water (negative control) and pimobendan solution. Plasma samples and noninvasive measures of cardiovascular function were obtained over a 24‐h period following dosing. Pimobendan and its active metabolite were quantified using an ultra‐high‐performance liquid chromatography–mass spectrometer (UHPLC‐MS) assay. The oral pimobendan solution was rapidly absorbed [time taken to reach maximum concentration (T_max) 1.1 h] and readily converted to the active metabolite (metabolite T_max 1.3 h). The elimination half‐life was short for both pimobendan and its active metabolite (0.9 and 1.6 h, respectively). Maximal cardiovascular effects occurred at 2–4 h after a single oral dose, with measurable effects occurring primarily in echocardiographic indices of systolic function. Significant effects persisted for <8 h. The pimobendan nonaqueous oral solution was well tolerated by study dogs.     

Pharmacokinetics and physiologic effects of alprazolam after a single oral dose in healthy mares

The objective of this study was to evaluate the pharmacokinetic properties and physiologic effects of a single oral dose of alprazolam in horses. Seven adult female horses received an oral administration of alprazolam at a dosage of 0.04 mg/kg body weight. Blood samples were collected at various time points and assayed for alprazolam and its metabolite, α‐hydroxyalprazolam, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of alprazolam was analyzed by a one‐compartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single‐dose administration of alprazolam were as follows: C_max 14.76 ± 3.72 ng/mL and area under the curve (AUC_0–∞) 358.77 ± 76.26 ng·h/mL. Median (range) T_max was 3 h (1–12 h). Alpha‐hydroxyalprazolam concentrations were detected in each horse, although concentrations were low (C_max 1.36 ± 0.28 ng/mL). Repeat physical examinations and assessment of the degree of sedation and ataxia were performed every 12 h to evaluate for adverse effects. Oral alprazolam tablets were absorbed in adult horses and no clinically relevant adverse events were observed. Further evaluation of repeated dosing and safety of administration of alprazolam to horses is warranted.     

Pharmacokinetics and bone tissue concentrations of lincomycin following intravenous and intramuscular administrations to cats

Albarellos, G. A., Montoya, L., Denamiel, G. A. A., Velo, M. C., Landoni, M. F. Pharmacokinetics and bone tissue concentrations of lincomycin following intravenous and intramuscular administrations to cats. J. vet. Pharmacol. Therap.  35 , 534–540. The pharmacokinetic properties and bone concentrations of lincomycin in cats after single intravenous and intramuscular administrations at a dosage rate of 10 mg/kg were investigated. Lincomycin minimum inhibitory concentration (MIC) for some gram‐positive strains isolated from clinical cases was determined. Serum lincomycin disposition was best‐fitted to a bicompartmental and a monocompartmental open models with first‐order elimination after intravenous and intramuscular dosing, respectively. After intravenous administration, distribution was rapid (T_1/2(d) = 0.22 ± 0.09 h) and wide as reflected by the volume of distribution (V_(d(ss))) of 1.24 ± 0.08 L/kg. Plasma clearance was 0.28 ± 0.09 L/h·kg and elimination half‐life (T_1/2) 3.56 ± 0.62 h. Peak serum concentration (C_max), T_max, and bioavailability for the intramuscular administration were 7.97 ± 2.31 μg/mL, 0.12 ± 0.05 h, and 82.55 ± 23.64%, respectively. Thirty to 45 min after intravenous administration, lincomycin bone concentrations were 9.31 ± 1.75 μg/mL. At the same time after intramuscular administration, bone concentrations were 3.53 ± 0.28 μg/mL. The corresponding bone/serum ratios were 0.77 ± 0.04 (intravenous) and 0.69 ± 0.18 (intramuscular). Lincomycin MIC for Staphylococcus spp. ranged from 0.25 to 16 μg/mL and for Streptococcus spp. from 0.25 to 8 μg/mL.     

Pharmacokinetics of meloxicam after intravenous,intramuscular and oral administration of a single dose to African grey parrots (Psittacus erithacus)

Meloxicam is a nonsteroidal anti‐inflammatory drug commonly used in avian species. In this study, the pharmacokinetic parameters for meloxicam were determined following single intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administrations of the drug (1 mg/kg·b.w.) in adult African grey parrots (Psittacus erithacus; n = 6). Serial plasma samples were collected and meloxicam concentrations were determined using a validated high‐performance liquid chromatography assay. A noncompartmental pharmacokinetic analysis was performed. No undesirable side effects were observed during the study. After i.v. administration, the volume of distribution, clearance and elimination half‐life were 90.6 ± 4.1 mL/kg, 2.18 ± 0.25 mL/h/kg and 31.4 ± 4.6 h, respectively. The peak mean ± SD plasma concentration was 8.32 ± 0.95 μg/mL at 30 min after i.m. administration. Oral administration resulted in a slower absorption (t_max = 13.2 ± 3.5 h; C_max = 4.69 ± 0.75 μg/mL) and a lower bioavailability (38.1 ± 3.6%) than for i.m. (78.4 ± 5.5%) route. At 24 h, concentrations were 5.90 ± 0.28 μg/mL for i.v., 4.59 ± 0.36 μg/mL for i.m. and 3.21 ± 0.34 μg/mL for p.o. administrations and were higher than those published for Hispaniolan Amazon parrots at 12 h with predicted analgesic effects.     

Pharmacokinetics of valnemulin after intravenous,intramuscular, and oral administration in layer chickens

The pharmacokinetic characteristics of valnemulin in layer chickens were studied after single intravenous, intramuscular, and oral administration at a dose of 15 mg/kg body weight. Plasma samples at certain time points were collected and the drug concentrations in them by ultra high‐performance liquid chromatography tandem mass spectrometry (UHPLC‐MS). The concentration–time data for each individual were plotted by noncompartmental analysis for the whole three routes. Following intravenous administration, the plasma concentration showed tiny fluctuation. The elimination half‐life (), total body clearance (Cl), and area under the plasma concentration–time curve (AUC) were 1.85 ± 0.43 h, 2.2 ± 0.9 L/h, and 7.52 ± 2.46 μg·h/mL, respectively. Following intramuscular administration, the peak concentration (C_max, 1.40 ± 0.43 μg/mL) was achieved at the time of 0.34 h. A multiple‐peak phenomenon existed after oral administration, and the first peak and secondary peak were at 10 min and during 2–4 h, respectively, while the tertiary peak appeared during 5–15 h. The bioavailability (F %) for intramuscular and oral administration was 68.60% and 52.64%, respectively. In present study, the detailed pharmacokinetic profiles showed that this drug is widely distributed and rapidly eliminated, however has a low bioavailability, indicating that valnemulin is likely to be a favorable choice in the clinical practice.     

Pharmacokinetics of ceftiofur sodium in cats following a single intravenous and subcutaneous injection

Ceftiofur, a third‐generation cephalosporin antibiotic, is being extensively used by pet doctors in China. In the current study, the detection method was developed for ceftiofur and its metabolites, desfuroylceftiofur (DCE) and desfuroylceftiofur conjugates (DCEC), in feline plasma. Then, the pharmacokinetics studies were performed following one single intravenous and subcutaneous injection of ceftiofur sodium in cats both at 5 mg/kg body weight (BW) (calculated as pure ceftiofur). Ceftiofur, DCE, and DCEC were extracted from plasma samples, then derivatized and further quantified by high‐performance liquid chromatography. The concentrations versus time data were subjected to noncompartmental analysis to obtain the pharmacokinetics parameters. The terminal half‐life (t_1/2λz) was calculated as 11.29 ± 1.09 and 10.69 ± 1.31 hr following intravenous and subcutaneous injections, respectively. After intravenous treatment, the total body clearance (Cl) and volume of distribution at steady‐state (V_SS) were determined as 14.14 ± 1.09 ml hr^‐1 kg^‐1 and 241.71 ± 22.40 ml/kg, respectively. After subcutaneous injection, the peak concentration (C_max; 14.99 ± 2.29 μg/ml) was observed at 4.17 ± 0.41 hr, and the absorption half‐life (t_1/2ka) and absolute bioavailability (F) were calculated as 2.83 ± 0.46 hr and 82.95%±9.59%, respectively. The pharmacokinetic profiles of ceftiofur sodium and its related metabolites demonstrated their relatively slow, however, good absorption after subcutaneous administration, poor distribution, and slow elimination in cats. Based on the time of drug concentration above the minimum inhibitory concentration (MIC) (T>MIC) calculated in the current study, an intravenous or subcutaneous dose at 5 mg/kg BW of ceftiofur sodium once daily is predicted to be effective for treating feline bacteria with a MIC value of ≤4.0 μg/ml.     

Detection,quantifications, and pharmacokinetics of ponazuril in healthy swine

A study on pharmacokinetics of ponazuril in piglets was conducted after a single oral dose of 5.0 mg/kg b.w. Plasma concentrations were measured by high‐performance liquid chromatography assay with UV detector at 255‐nm wavelength. Pharmacokinetic parameters were derived by use of a standard noncompartmental pharmacokinetic analysis. Samples from six piglets showed good plasma concentrations of ponazuril, which peaked at 5.83 ± 0.94 μg/mL. Mean ± SD area under the plasma concentration–time curve was 1383.42 ± 363.26 h/μg/mL, and the elimination half‐life was 135.28 ± 19.03 h. Plasma concentration of ponazuril peaked at 42 h (range, 36–48 h) after administration and gradually decreased but remained detectable for up to 33 days. No adverse effects were observed during the study period. The results indicate that ponazuril was relatively well absorbed following a single dose, which makes ponazuril likely to be effective in swine.     

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).     

Pharmacokinetic profiles of florfenicol in spotted halibut,Verasper variegatus,at two water temperatures

The pharmacokinetic profiles of florfenicol in the spotted halibut (Verasper variegatus) were investigated at 15 and 20°C water temperatures, respectively. Florfenicol content in plasma samples was analyzed using an HPLC method. Drug concentration versus time data were best fitted to a three‐compartment model after a single intravenous administration (15 mg/kg BW), and fitted to a two‐compartment model after an oral administration (30 mg/kg BW) at 15 and 20°C. The florfenicol concentration in the blood increased slowly during the 12 hr following an oral administration at 15°C, with a peak concentration (C_max) of 9.1 mg/L, and then declined gradually. The half‐lives of absorption, distribution, and elimination phase were 2.18, 5.66 and 14.25 hr, respectively. The bioavailability (F) was calculated to be 24.14%. After an oral administration at 20°C, shorter half‐lives of absorption (1.33 hr), distribution (2.51 hr) and elimination (9.71 hr), a higher C_max (12.2 mg/L), and a similar F (23.98%) were found. Based on the pharmacokinetics and pharmacodynamics, an oral dose of 30 mg/kg BW was suggested to be efficacious for bacterial disease control in spotted halibut farming.     

Pharmacokinetics of the novel COX‐2 selective inhibitor vitacoxib in cats: The effects of feeding and dose

The purpose of this study was to determine the pharmacokinetics and dose‐scaling model of vitacoxib in either fed or fasted cats following either oral or intravenous administration. The concentration of the drug was quantified by UPLC‐MS/MS on plasma samples. Relevant parameters were described using noncompartmental analysis (WinNonlin 6.4 software). Vitacoxib is relatively slowly absorbed and eliminated after oral administration (2 mg/kg body weight), with a T_max of approximately 4.7 hr. The feeding state of the cat was a statistically significant covariate for both area under the concentration versus time curve (AUC) and mean absorption time (MAT_fed). The absolute bioavailability (F) of vitacoxib (2 mg/kg body weight) after oral administration (fed) was 72.5%, which is higher than that in fasted cats (F = 50.6%). Following intravenous administration (2 mg/kg body weight), Vd (ml/kg) was 1,264.34 ± 343.63 ml/kg and Cl (ml kg^?1 hr^?1) was 95.22 ± 23.53 ml kg^?1 hr^?1. Plasma concentrations scaled linearly with dose, with C_max (ng/ml) of 352.30 ± 63.42, 750.26 ± 435.54, and 936.97 ± 231.27 ng/ml after doses of 1, 2, and 4 mg/kg body weight, respectively. No significant undesirable behavioral effects were noted throughout the duration of the study.     

Pharmacokinetics of procaterol in thoroughbred horses

Procaterol (PCR) is a beta‐2‐adrenergic bronchodilator widely used in Japanese racehorses for treating lower respiratory disease. The pharmacokinetics of PCR following single intravenous (0.5 μg/kg) and oral (2.0 μg/kg) administrations were investigated in six thoroughbred horses. Plasma and urine concentrations of PCR were measured using liquid chromatography–mass spectrometry. Plasma PCR concentration following intravenous administration showed a biphasic elimination pattern. The systemic clearance was 0.47 ± 0.16 L/h/kg, the steady‐state volume of the distribution was 1.21 ± 0.23 L/kg, and the elimination half‐life was 2.85 ± 1.35 h. Heart rate rapidly increased after intravenous administration and gradually decreased thereafter. A strong correlation between heart rate and plasma concentration of PCR was observed. Plasma concentrations of PCR after oral administration were not quantifiable in all horses. Urine concentrations of PCR following intravenous and oral administrations were quantified in all horses until 32 h after administration. Urine PCR concentrations were not significantly different on and after 24 h between intravenous and oral administrations. These results suggest that the bioavailability of orally administrated PCR in horses is very poor, and the drug was eliminated from the body slowly based on urinary concentrations. This report is the first study to demonstrate the pharmacokinetic character of PCR in thoroughbred horses.     

Pharmacokinetics of ceftiofur sodium in Peekapoo dogs following a single intravenous and subcutaneous injection

The present study aimed to determine the pharmacokinetic profiles of ceftiofur (as measured by ceftiofur and its active metabolites concentrations) in a small-size dog breed, Peekapoo, following a single intravenous or subcutaneous injection of ceftiofur sodium. The study population comprised of five clinically healthy Peekapoo dogs with an average body weight (BW) of 3.4 kg. Each dog received either intravenous or subcutaneous injection, both at 5 mg/kg BW (calculated as pure ceftiofur). Plasma samples were collected at different time points after the administration. Ceftiofur and its active metabolites were extracted from plasma samples, derivatized, and further quantified by high-performance liquid chromatography. The concentrations versus time data were subjected to noncompartmental analysis to obtain the pharmacokinetic parameters. The terminal half-life (t_1/2λz) was calculated as 7.40 ± 0.79 and 7.91 ± 1.53 hr following intravenous and subcutaneous injections, respectively. After intravenous treatment, the total body clearance (Cl) and volume of distribution at steady-state (V_SS) were determined as 39.91 ± 4.04 ml hr⁻¹ kg⁻¹ and 345.71 ± 28.66 ml/kg, respectively. After subcutaneous injection, the peak concentration (C_max; 10.50 ± 0.22 μg/ml) was observed at 3.2 ± 1.1 hr, and the absorption half-life (t_1/2ka) and absolute bioavailability (F) were calculated as 0.74 ± 0.23 hr and 91.70%±7.34%, respectively. The pharmacokinetic profiles of ceftiofur and its related metabolites demonstrated their quick and excellent absorption after subcutaneous administration, in addition to poor distribution and slow elimination in Peekapoo dogs. Based on the time of concentration above minimum inhibitory concentration (T > MIC) values calculated here, an intravenous or subcutaneous dose at 5 mg/kg of ceftiofur sodium once every 12 hr is predicted to be effective for treating canine bacteria with a MIC value of ≤4.0 μg/ml.     

Pharmacokinetics of levofloxacin after single intravenous,oral and subcutaneous administration to dogs

The pharmacokinetic properties of the fluoroquinolone levofloxacin (LFX) were investigated in six dogs after single intravenous, oral and subcutaneous administration at a dose of 2.5, 5 and 5 mg/kg, respectively. After intravenous administration, distribution was rapid (T_½dist 0.127 ± 0.055 hr) and wide as reflected by the volume of distribution of 1.20 ± 0.13 L/kg. Drug elimination was relatively slow with a total body clearance of 0.11 ± 0.03 L kg^?1 hr^?1 and a T_½ for this process of 7.85 ± 2.30 hr. After oral and subcutaneous administration, absorption half‐life and T_max were 0.35 and 0.80 hr and 1.82 and 2.82 hr, respectively. The bioavailability was significantly higher (p ? 0.05) after subcutaneous than oral administration (79.90 vs. 60.94%). No statistically significant differences were observed between other pharmacokinetic parameters. Considering the AUC_24 hr/MIC and C_max/MIC ratios obtained, it can be concluded that LFX administered intravenously (2.5 mg/kg), subcutaneously (5 mg/kg) or orally (5 mg/kg) is efficacious against Gram‐negative bacteria with MIC values of 0.1 μg/ml. For Gram‐positive bacteria with MIC values of 0.5 μg/kg, only SC and PO administration at a dosage of 5 mg/kg showed to be efficacious. MIC‐based PK/PD analysis by Monte Carlo simulation indicates that the proposed dose regimens of LFX, 5 and 7.5 mg/kg/24 hr by SC route and 10 mg/kg/24 hr by oral route, in dogs may be adequate to recommend as an empirical therapy against S. aureus strains with MIC ≤ 0.5 μg/ml and E. coli strains with MIC values ≤0.125 μg/ml.