Reduction in pain response by combined use of local lidocaine anesthesia and systemic ketoprofen in dairy calves dehorned by heat cauterization

This study assessed the efficacy of ketoprofen for mitigating pain following dehorning with an electric cautery iron. Forty Holstein heifer calves, 4 to 8 wk of age, were randomized to receive a lidocaine cornual nerve block and either an injection of ketoprofen (3 mg/kg IM) or physiological saline, 10 min prior to dehorning. Cortisol was measured from serum obtained 10 min prior to dehorning and at 3 and 6 h post-dehorning. Calf behavior was video-recorded between 0 to 2, 3 to 5, and 6 to 8 h post-dehorning, and frequency of ear flicks, head shakes, head rubs, lying, standing, feeding, and grooming were recorded. Finally, 24-h intake of calf starter was recorded. There was no effect of treatment on cortisol (P > 0.1); however, ketoprofen-treated calves displayed less ear-flicks and total head behavior (P < 0.05), and tended to consume more starter (P = 0.09) than control calves. Ketoprofen is effective for mitigating behavioral effects of postsurgical pain following dehorning in 4- to 8-week-old calves.     

Disodium-fosfomycin pharmacokinetics and bioavailability in post weaning piglets

Disodium-fosfomycin pharmacokinetics has been studied in different species after oral, intravenous, intramuscular and subcutaneous administration. At present there are neither documented clinical experiences of the use of fosfomycin in pigs nor any published studies in weaning piglets, although it is a period of high incidence of infectious diseases. The pharmacokinetics and the bioavailability of sodium fosfomycin were studied in post weaning piglets after intravenous and intramuscular administration of 15 mg/kg of body weight. Plasma concentrations were measured by a high-performance liquid ms/ms. After IV administration the area under the fosfomycin concentration:time curve in plasma was AUC_(0–12) of 120.00 ± 23.12 μg h/ml and the volume of distribution (Vd) of 273.00 ± 40.70 ml/kg. The elimination was rapid with a plasma clearance of 131.50 ± 30.07 ml/kg/h and a T_1/2 of 1.54 ± 0.40 h. Peak serum concentration (C_max), T_max, AUC_(0–12) and bioavailability for the IM administration were 43.00 ± 4.10 μg/ml, 0.75 ± 0.00 h, 99.00 ± 0.70 μg h/ml and 85.5 ± 9.90% respectively. Different authors have determined a minimum inhibitory concentration (MIC₉₀) ranging from 0.25 μg/ml for Streptococcus sp. and 0.5 μg/ml for Escherichia coli. Considering the above, and according to the values of plasma concentration vs time profiles observed in this study, effective plasma concentrations of fosfomycin for sensitive bacteria can be obtained following IV and IM administration of 15 mg/kg in piglets.     

Ketoprofen pharmacokinetics of R‐ and S‐isomers in juvenile loggerhead sea turtles (Caretta caretta) after single intravenous and single‐ and multidose intramuscular administration

Ketoprofen is a nonsteroidal anti‐inflammatory and analgesic agent that nonselectively inhibits cyclooxygenase, with both COX‐1 and COX‐2 inhibition. Recent studies on COX receptor expression in reptiles suggest that nonselective COX inhibitors may be more appropriate than more selective inhibitors in some reptiles, but few pharmacokinetic studies are available. The goal of this study was to determine single‐ and multidose (three consecutive days) pharmacokinetics of racemic ketoprofen administered intravenously and intramuscularly at 2 mg/kg in healthy juvenile loggerhead turtles (Caretta caretta). The S‐isomer is the predominant isomer in loggerhead sea turtles, similar to most mammals, despite administration of a 50:50 racemic mixture. Multidose ketoprofen administration demonstrated no bioaccumulation; therefore, once‐daily dosing will not require dose adjustment over time. S‐isomer pharmacokinetic parameters determined in this study were C_max of 10.1 μg/ml by IM injection, C₀ of 13.4 μg/ml by IV injection, AUC of 44.7 or 69.4 μg*hr/ml by IM or IV injection, respectively, and T½ of 2.8 or 3.6 hr by IM or IV injection, respectively. Total ketoprofen plasma concentrations were maintained for at least 12 hr above concentrations determined to be effective for rats and humans. A dose of 2 mg/kg either IM or IV every 24 hr is likely appropriate for loggerhead turtles.     

Enantiospecific ketoprofen concentrations in plasma after oral and intramuscular administration in growing pigs

Background

Ketoprofen is a non-steroidal anti-inflammatory drug which has been widely used for domestic animals. Orally administered racemic ketoprofen has been reported to be absorbed well in pigs, and bioavailability was almost complete. The objectives of this study were to analyze R- and S-ketoprofen concentrations in plasma after oral (PO) and intra muscular (IM) routes of administration, and to assess the relative bioavailability of racemic ketoprofen for both enantiomers between those routes of administration in growing pigs.

Methods

Eleven pigs received racemic ketoprofen at dose rates of 4 mg/kg PO and 3 mg/kg IM in a randomized, crossover design with a 6-day washout period. Enantiomers were separated on a chiral column and their concentrations were determined by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated and relative bioavailability (F_rel) was determined for S and R –ketoprofen.

Results

S-ketoprofen was the predominant enantiomer in pig plasma after administration of the racemic mixture via both routes. The mean (± SD) maximum S-ketoprofen concentration in plasma (7.42 mg/L ± 2.35 in PO and 7.32 mg/L ± 0.75 in IM) was more than twice as high as that of R-ketoprofen (2.55 mg/L ± 0.99 in PO and 3.23 mg/L ± 0.70 in IM), and the terminal half-life was three times longer for S-ketoprofen (3.40 h ± 0.91 in PO and 2.89 h ± 0.85 in IM) than R-ketoprofen (1.1 h ± 0.90 in PO and 0.75 h ± 0.48 in IM). The mean (± SD) relative bioavailability (PO compared to IM) was 83 ± 20% and 63 ± 23% for S-ketoprofen and R-ketoprofen, respectively.

Conclusions

Although some minor differences were detected in the ketoprofen enantiomer concentrations in plasma after PO and IM administration, they are probably not relevant in clinical use. Thus, the pharmacological effects of racemic ketoprofen should be comparable after intramuscular and oral routes of administration in growing pigs.     

Evaluation of bioequivalence after oral, intramuscular, and intravenous administration of racemic ketoprofen in pigs

OBJECTIVE: To assess bioequivalence after oral, IM, and IV administration of racemic ketoprofen in pigs and to investigate the bioavailability after oral and IM administration. ANIMALS: 8 crossbred pigs. PROCEDURES: Each pig received 4 treatments in a randomized crossover design, with a 6-day washout period. Ketoprofen was administered at 3 and 6 mg/kg, PO; 3 mg/kg, IM; and 3 mg/kg, IV. Plasma ketoprofen concentrations were measured by use of high-performance liquid chromatography for up to 48 hours. To assess bioequivalence, a 90% confidence interval was calculated for the area under the time-concentration curve (AUC) and maximum plasma concentration (C(max)). RESULTS: Equivalence was not detected in the AUCs among the various routes of administration nor in C(max) between oral and IM administration of 3 mg/kg. The bioavailability of ketoprofen was almost complete after each oral or IM administration. Mean +/- SD C(max) was 5.09 +/- 1.41 microg/mL and 7.62 +/- 1.22 microg/mL after oral and IM doses of 3 mg/kg, respectively. Mean elimination half-life varied from 3.52 +/- 0.90 hours after oral administration of 3 mg/kg to 2.66 +/- 0.50 hours after IV administration. Time to peak C(max) after administration of all treatments was approximately 1 hour. Increases in AUC and C(max) were proportional when the orally administered dose was increased from 3 to 6 mg/kg. Conclusions and Clinical Relevance: Orally administered ketoprofen was absorbed well in pigs, although bioequivalence with IM administration of ketoprofen was not detected. Orally administered ketoprofen may have potential for use in treating pigs.     

Pharmacokinetics and pharmacodynamics of alfaxalone after a single intramuscular or intravascular injection in mallard ducks (Anas platyrhynchos)

Pharmacokinetics and pharmacodynamics of alfaxalone was performed in mallard ducks (Anas platyrhynchos) after single bolus injections of 10 mg/kg administered intramuscularly (IM; n = 10) or intravenously (IV; n = 10), in a randomized cross‐over design with a washout period between doses. Mean (±SD) C_max following IM injection was 1.6 (±0.8) µg/ml with T_max at 15.0 (±10.5) min. Area under the curve (AUC) was 84.66 and 104.58 min*mg/ml following IV and IM administration, respectively. Volume of distribution (V_D) after IV dose was 3.0 L/kg. The mean plasma clearance after 10 mg/kg IV was 139.5 (±67.9) ml min^?1 kg^?1. Elimination half‐lives (mean [±SD]) were 15.0 and 16.1 (±3.0) min following IV and IM administration, respectively. Mean bioavailability at 10 mg/kg IM was 108.6%. None of the ducks achieved a sufficient anesthetic depth for invasive procedures, such as surgery, to be performed. Heart and respiratory rates measured after administration remained stable, but many ducks were hyperexcitable during recovery. Based on sedation levels and duration, alfaxalone administered at dosages of 10 mg/kg IV or IM in mallard ducks does not induce clinically acceptable anesthesia.     

Pharmacokinetics of enrofloxacin and danofloxacin in premature calves

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

Pharmacokinetics and bioavailability of carbetocin after intravenous and intramuscular administration in cows and gilts

The pharmacokinetics of carbetocin, which is used to control postpartum hemorrhage after giving birth, was studied in cows and gilts after a single intravenous (IV) or intramuscular (IM) injection. Blood samples from animals were assessed by oxytocin radioimmunoassay, and then the pharmacokinetic parameters were calculated using a noncompartmental model. For gilts, there was no significant difference between half-life (T_1/2λZ), mean residue time (MRT), and maximum concentration (C_max) between IM and IV administration. Conversely, the time to reach the C_max (T_max) and MRT were higher following administration of 350 μg/animal in cows via the IM administration compared with IV. The longest T_1/2λZ was 0.85 hr, indicating carbetocin was absorbed and eliminated rapidly in both animal species after administration. The T_max was similar between cows and gilts following IM administration. Moreover, the C_max after IM injection was about half that of IV administration in both animals. The bioavailability was more than 80% in cows, suggesting administration via the IM route is efficient. This is in agreement with the longer T_1/2λZ in cows after IM administration. However, the IV route is recommended for gilts due to a lower bioavailability (35%) and shorter T_1/2λZ after IM administration compared with IV.     

Pharmacokinetics and bioavailability of doxycycline in ostriches (Struthio camelus) at two different dose rates

A bioavailability and pharmacokinetics study of doxycycline was carried out on 30 healthy ostriches after a single intravenous (IV), intramuscular (IM) and oral dose of 15 mg/kg body weight. The plasma doxycycline concentration was determined by HPLC/UV at 0 (pretreatment), 0.08, 0.25, 0.5 1, 2, 4, 6, 8, 12, 24 and 48 h after administration. The plasma concentration-time curves were examined using non-compartmental methods based on the statistical moment theory for only the higher dose. After IV administration, the elimination half-life (t_1/2β), mean residence time (MRT), volume of distribution at the steady-state (V_ss), volume of distribution (Vd_area) and total body clearance (Cl_B) were 7.67 ± 0.62 h, 6.68 ± 0.86 h, 0.86 ± 0.16 l/kg, 1.67 ± 0.52 l/kg and 2.51 ± 0.63 ml/min/kg, respectively. After IM and oral dosing, the mean peak plasma concentrations (C_max) were 1.34 ± 0.33 and 0.30 ± 0.04 µg/ml, respectively, which were achieved at a post-administration time (t_max) of 0.75 ± 0.18, 3.03 ± 0.48 h, respectively. The t_1/2β, Vd_area and Cl_B after IM administration were 25.02 ± 3.98 h, 23.99 ± 3.4 l/kg and 12.14 ± 1.71 ml/min/kg, respectively and 19.25 ± 2.53 h, 61.49 ± 7 l/kg and 40.19 ± 3.79 ml/min/kg after oral administration, respectively. The absolute bioavailability (F) of doxycycline was 5.03 and 17.52% after oral and IM administration, respectively. These results show that the dose data from other animals particularly mammals cannot be extrapolated to ostriches. Therefore, based on these results along with those reported in the literature, further studies on the pharmacokinetic/pharmacodynamic, in vitro minimum inhibitory concentration values and clinical applications of doxycycline in ostriches are required.     

Pharmacokinetics of injectable marbofloxacin after intravenous and intramuscular administration in red-eared sliders (Trachemys scripta elegans)

Fluoroquinolone antibacterial drugs are currently used in reptilian medicine because of their broad spectrum of activity including the most frequent pathogens of these species. The disposition kinetics of marbofloxacin (MBX) at a single dose of 2 mg/kg were determined in healthy red-eared sliders after intravenous (IV) and intramuscular (IM) administration. The influence of renal portal system on the bioavailability of the drug was investigated by using forelimb and hindlimb as IM injection sites. Apparent volume of distribution at steady-state (V_ss) and systemic clearance (Cl) of marbofloxacin after IV administration were estimated to be 48.21 ± 5.42 ml/kg and 23.38 ± 2.90 ml/hr·kg, respectively. The absolute bioavailabilities after IM route were 45.96% (forelimb) and 52.09% (hindlimb). The lack of statistically significant differences in most of the pharmacokinetic parameters after the two IM injection sites suggests a negligible influence of renal portal system in clinical use of MBX, although the C_max after IM_fore administration is advantageous, having into account the concentration-dependent action of this antibiotic. The absence of visible adverse reactions in the animals and the advantageous pharmacokinetic properties suggest the possibility of its safe and effective clinical use in red-eared sliders.     

Comparison of oral versus parenteral iron supplementation on the health and productivity of piglets

The aim of this study was to compare oral iron supplementation in feed with a standard iron injection and assess the impact on the health and productivity of pigs. The reliability of a quick test (HemoCue) for the measurement of blood haemoglobin concentration was also investigated. Three pig herds, with a total of 88 sows and their piglets, were included in the study. Piglets in treatment group O were fed a special iron-rich feed on days 2 to 4, 5 to 7 and 8 to 12 of lactation using a specially designed feeding device. Piglets in group IM received 200 mg of an iron dextran complex intramuscularly at three days of age. Haemoglobin concentrations and performance of the piglets were compared between groups. The mean haemoglobin concentrations in pigs at weaning were 131.4 and 116.4 g/l for pigs in groups O and IM, respectively (P<0.01). Daily weight gain (253.9 v 248.8 g/day) and piglet mortality (11.4 v 12.2 per cent) were slightly better in group O than in group IM (P>0.05).     

Pharmacokinetics of cefquinome in red‐eared slider turtles (Trachemys scripta elegans) after single intravenous and intramuscular injections

The purpose of this study was to evaluate the pharmacokinetics of cefquinome (CFQ ) following single intravenous (IV ) or intramuscular (IM ) injections of 2 mg/kg body weight in red‐eared slider turtles. Plasma concentrations of CFQ were determined by high‐performance liquid chromatography and analyzed using noncompartmental methods. The pharmacokinetic parameters following IV injection were as follows: elimination half‐life (t _1/2λz) 21.73 ± 4.95 hr, volume of distribution at steady‐state (V _dss) 0.37 ± 0.11 L/kg, area under the plasma concentration–time curve (AUC _0–∞) 163 ± 32 μg hr^?1 ml^?1, and total body clearance (Cl_T) 12.66 ± 2.51 ml hr^?1 kg^?1. The pharmacokinetic parameters after IM injection were as follows: peak plasma concentration (C _max) 3.94 ± 0.84 μg/ml, time to peak concentration (T _max) 3 hr, t _1/2λz 26.90 ± 4.33 hr, and AUC _0–∞ 145 ± 48 μg hr^?1 ml^?1. The bioavailability after IM injection was 88%. Data suggest that CFQ has a favorable pharmacokinetic profile with a long half‐life and a high bioavailability in red‐eared slider turtles. Further studies are needed to establish a multiple dosage regimen and evaluate clinical efficacy.     

Pharmacokinetics,bioavailability and PK/PD relationship of cefquinome for Escherichia coli in Beagle dogs

The pharmacokinetics and bioavailability of cefquinome in Beagle dogs were determined by intravenous (IV), intramuscular (IM) or subcutaneous (SC) injection at a single dose of 2 mg/kg body weight (BW). The minimum inhibitory concentrations (MIC) of cefquinome against 217 Escherichia coli isolated from dogs were also investigated. After IV injection, the plasma concentration‐time curve of cefquinome was analyzed using a two‐compartmental model, and the mean values of t_1/2α (h), t_1/2β (h), V_ss (L/kg), Cl_B (L/kg/h) and AUC (μg·h/mL) were 0.12, 0.98, 0.30, 0.24 and 8.51, respectively. After IM and SC administration, the PK data were best described by a one‐compartmental model with first‐order absorption. The mean values of t_1/2Kel, t_1/2Ka, t_max (h), C_max (μg/mL) and AUC (μg·h/mL) were corresponding 0.85, 0.14, 0.43, 4.83 and 8.24 for IM administration, 0.99, 0.29, 0.72, 3.88 and 9.13 for SC injection. The duration of time that drug levels exceed the MIC (%T > MIC) were calculated using the determined MIC₉₀ (0.125 μg/mL) and the PK data obtained in this study. The results indicated that the dosage regimen of cefquinome at 2 mg/kg BW with 12‐h intervals could achieve %T > MIC above 50% that generally produced a satisfactory bactericidal effect against E. coli isolated from dogs in this study.     

Comparative Pharmacokinetics and bioavailability of marbofloxacin in geese (Anser Anser domesticus) after two sites of intramuscular administrations

The pharmacokinetics of marbofloxacin (MAR) was compared in geese (Anser Anser domesticus) after single intravenous (IV) and intramuscular (IM) (thigh and pectoral muscles) administrations of 5 mg/kg. Serum concentrations of MAR were determined with high-performance liquid chromatography (HPLC) method. Serum MAR concentrations versus time were analyzed by a noncompartmental method. After IV administration, MAR showed high volume of distribution at steady state (V_dss) of 5.24 ± 1.08 L/kg. The serum body clearance (Cl) and elimination half-life (T_1/2λz) of MAR were 0.79 ± 0.07 L hr⁻¹ kg⁻¹ and 6.94 ± 1.12 hr, respectively. The peak of MAR serum concentrations C_max achieved at one and 0.50 hr after thigh and pectoral IM sites of injections, respectively, were 1.20 and 0.91 μg/ml. Significant differences were found in the mean absorption time (MAT), the systemic bioavailability (F%), and elimination parameters of MAR between two sites of injections, indicating that the absorption was fairly slow and complete after thigh IM injection. The pharmacokinetics of MAR in geese diverged according to the site of IM injection following a parallel study design. We recommend the thigh muscle as IM site of injection to obtain maximum concentrations of the administered drug in geese.     

肌注补铁对仔猪增重和血红蛋白含量的影响

9头经产长白母猪生产的37头仔猪分成三组来评价在不同日龄肌肉注射不同剂量的铁对仔猪增重和血红蛋白含量的影响。试验Ⅰ组的13头仔猪3日龄一次肌注150毫克铁,30日龄体重达8.22公斤;血红蛋白由初生6小时的8.20克/100毫升血液下降到了3日龄的6.32克,然后逐渐升高,10日龄后趋于并稳定在8.0克左右。试验Ⅱ组的13头仔猪分别在3、10、17日龄三次肌注150毫克(每次50mg)铁,30日龄体重为7.79公斤;血红蛋白由生后6小时的3.54克持续下降到10日龄的5.40克,然后逐渐恢复升高,17日龄后趋近稳定在8.0克左右。试验Ⅲ组的11头仔猪分别在7、15日龄二次肌注100毫克(每次50毫克)铁,增重速度最慢,30日龄体重才7.14公斤,血红蛋白由生后6小时的8.84克持续下降到17日龄的5.09克,然后逐渐恢复,31日龄趋于8.0克。试验表明,3日龄一次大剂量(150毫克)肌注补铁对哺乳仔猪早期增重有利,从而避免缺铁性贫血。8.0克或以上是仔猪血红蛋白含量的正常值,表明铁给量适当,生长正常,低于6.0克是哺乳仔猪缺铁的判断指标。     

Pharmacokinetics of a single intramuscular injection of cefquinome in buffalo calves

The objective of this study was to investigate the pharmacokinetics of cefquinome following single intramuscular (IM) administration in six healthy male buffalo calves. Cefquinome was administered intramuscularly (2 mg/kg bodyweight) and blood samples were collected prior to drug administration and up to 24 hr after injection. No adverse effects or changes were observed after the IM injection of cefquinome. Plasma concentrations of cefquinome were determined by high‐performance liquid chromatography. The disposition of plasma cefquinome is characterized by a mono‐compartmental open model. The pharmacokinetic parameters after IM administration (mean ± SE) were C_max 6.93 ± 0.58 μg/ml, T_max 0.5 hr, t_½kα 0.16 ± 0.05 hr, t_½β 3.73 ± 0.10 hr, and AUC 28.40 ± 1.30 μg hr/ml after IM administration. A dosage regimen of 2 mg/kg bodyweight at 24‐hr interval following IM injection of cefquinome would maintain the plasma levels required to be effective against the bacterial pathogens with MIC values ≤0.39 μg/ml. The suggested dosage regimen of cefquinome has to be validated in the disease models before recommending for clinical use in buffalo calves.     

Pharmacokinetics of levamisole in the red‐eared slider turtles (Trachemys scripta elegans)

The pharmacokinetics and bioavailability of levamisole were determined in red‐eared slider turtles after single intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration. Nine turtles received levamisole (10 mg/kg) by each route in a three‐way crossover design with a washout period of 30 days. Blood samples were collected at time 0 (pretreatment), and at 0.25, 0.5, 1, 1.5, 3, 6, 9, 12, 18, 24, 36, and 48 hr after drug administration. Plasma levamisole concentrations were determined by a high‐performance liquid chromatography assay. Data were analyzed by noncompartmental methods. The mean elimination half‐life was 5.00, 7.88, and 9.43 hr for IV, IM, and SC routes, respectively. The total clearance and volume of distribution at steady state for the IV route were 0.14 L hr^?1 kg^?1 and 0.81 L/kg, respectively. For the IM and SC routes, the peak plasma concentration was 9.63 and 10.51 μg/ml, respectively, with 0.5 hr of T_max. The bioavailability was 93.03 and 115.25% for the IM and SC routes, respectively. The IM and SC route of levamisole, which showed the high bioavailability and long t_1/2?z, can be recommended as an effective way for treating nematodes in turtles.     

Pharmacokinetics of tramadol and its major metabolite after intramuscular administration in piglets

Tramadol (T) is a centrally acting atypical opioid used for treatment of dogs. Piglets might experience pain following castration, tooth clipping and tail docking and experimental procedures. The aim of this study was to assess the pharmacokinetics of T and its active metabolite M1 in male piglets after a single intramuscular injection. Six healthy male piglets were administered T (5 mg/kg) intramuscularly. Blood was sampled at scheduled time intervals and drug plasma concentrations evaluated by a validated HPLC method. T plasma concentration was quantitatively detectable from 0.083 to 8 h. M1 was quantified over a shorter time period (0.083–6 h) with a T_max at 0.821 h. The study demonstrated that piglets produce a larger amount of M1 compared with dogs, horses and goats. The human minimum effective concentration of M1 (40 ng/mL) was exceeded for over 3 h in piglets. If it is assumed to also apply to piglets, it could be speculated that the drug efficacy might exert its action over 3 h or longer. This assumption has to be confirmed by further specific pharmacokinetic/pharmacodynamic studies.     

Pharmacokinetics and bioavailability of cefquinome and ceftriaxone in premature calves

The aim of this study was to evaluate the pharmacokinetics and bioavailability of cefquinome (CFQ) and ceftriaxone (CTX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. Using a parallel design, 24 premature calves were randomly divided into the two antibiotic groups. Each of the six animals in the first group received CFQ (2 mg/kg) through IV or IM administration. The second group received CTX (20 mg/kg) via the same administration route. Plasma concentrations of the drugs were analyzed by high‐performance liquid chromatography and noncompartmental methods. Mean pharmacokinetic parameters of CFQ and CTX following IV administration were as follows: elimination half‐life (t_1/2λz) 1.85 and 3.31 hr, area under the plasma concentration–time curve (AUC_0–∞) 15.74 and 174 hr * μg/ml, volume of distribution at steady‐state 0.37 and 0.45 L/kg, and total body clearance 0.13 and 0.12 L hr^?1 kg^?1, respectively. Mean pharmacokinetic parameters of CFQ and CTX after IM injection were as follows: peak concentration 4.56 and 25.04 μg/ml, time to reach peak concentration 1 and 1.5 hr, t_1/2λz 4.74 and 3.62 hr, and AUC_0–∞ 22.75 and 147 hr * μg/ml, respectively. The bioavailability of CFQ and CTX after IM injection was 141% and 79%, respectively. IM administration of CFQ (2 mg/kg) and CTX (20 mg/kg) can be recommended at 12‐hr interval for treating infections caused by susceptible bacteria, with minimum inhibitory concentration values of ≤0.5 and ≤4 μg/ml, respectively, in premature calves. However, further research is indicated to assess the pharmacokinetic parameters following multiple doses of the drug in premature calves.     

Species comparison of enantioselective oral bioavailability and pharmacokinetics of ketoprofen

As a part of ongoing research to further elucidate frequent and species-specific causes of differences in oral bioavailability, a 3 mg/kg dose of racemic ketoprofen, a high permeability/low solubility compound in the human biopharmaceutics classification system, was administered intravenously and orally to different species. Due to possible enantioselective disposition kinetics and inversion, enantiomers were quantitated separately using a stereospecific HPLC assay. The absolute bioavailability of R(−) and S(+) ketoprofen in chickens, turkeys, dogs and pigs was 31.5% and 52.6%, 42.6% and 32.5%, 33.6% and 89.1%, and 85.9% and 83.5% respectively. Incomplete bioavailability in poultry is probably due to incomplete absorption in addition to first-pass elimination. Low bioavailability of R(−) ketoprofen in dogs, strongly indicates first-pass metabolism. High bioavailability of S(+) ketoprofen in dogs and both enantiomers in pigs confirms that absorption of these substances is complete and controlled by gastric emptying rather than dissolution.