Pharmacokinetics and plasma concentrations of acetylsalicylic acid after intravenous, rectal, and intragastric administration to horses

Six healthy adult horses (5 mares and 1 stallion) were given a single dose of acetylsalicylic acid (ASA), 20 mg/kg of body weight, by intravenous (IV), rectal, and intragastric (IG) routes. Serial blood samples were collected via jugular venipuncture over a 36-h period, and plasma ASA and salicylic acid (SA) concentrations were determined by high-performance liquid chromatography. After IV administration, the mean elimination rate constant of ASA (± the standard error of the mean) was 1.32 ± 0.09 h⁻l, the mean elimination half-life was 0.53 ± 0.04 h, the area under the plasma concentration-versus-time curve (AUC) was 2555 ± 98 μg · min/mL, the plasma clearance was 472 ± 18.9 mL/h/kg, and the volume of distribution at steady state was 0.22 ± 0.01 L/kg. After rectal administration, the plasma concentration of ASA peaked at 5.05 ± 0.80 μg/mL at 0.33 h, then decreased to undetectable levels by 4 h; the plasma concentration of SA peaked at 17.39 ± 5.46 μg/mL at 2 h, then decreased to 1.92 ± 0.25 μg/mL by 36 h. After rectal administration, the AUC for ASA was 439.4 ± 94.55 μg · min/mL and the bioavailability was 0.17 ± 0.037. After IG administration, the plasma concentration of ASA peaked at 1.26 ± 0.10 μg/mL at 0.67 h, then declined to 0.37 ± 0.37 μg/mL by 36 h; the plasma concentration of SA peaked at 23.90 ± 4.94 μg/mL at 4 h and decreased to 0.85 ± 0.31 μg/mL by 36 h. After IG administration, the AUC for ASA was 146.70 ± 24.90 μg · min/mL and the bioavailability was 0.059 ± 0.013. Administration of a single rectal dose of ASA of 20 mg/kg to horses results in higher peak plasma ASA concentrations and greater bioavailability than the same dose given IG. Plasma ASA concentrations after rectal administration should be sufficient to inhibit platelet thromboxane production, and doses lower than those suggested for IG administration may be adequate.     

The relative plasma availabilities of ivermectin in reindeer (Rangifer tarandus tarandus) following subcutaneous and two different oral formulation applications

Background

Overwintering (breeding) reindeer (Rangifer tarandus tarandus) are commonly treated with ivermectin against parasitic infestations once yearly in autumn-winter roundups. The only preparations registered to reindeer are those for subcutaneous injection. However, also oral extra-label ivermectin administration is used. Twenty-six, 8-month-old reindeer calves were randomly allocated into three groups. Group 1 (n = 9) received oral ivermectin mixture (Ivomec® vet mixt. 0.8 mg/ml, oral ovine liquid drench formulation), Group 2 (n = 9) oral ivermectin paste (Ivomec® vet 18.7 mg/g equine paste), and Group 3 (n = 8) subcutaneous injection of ivermectin (Ivomec® 10 mg/ml vet inj.), each group at a dose of 200 μg/kg body weight. Blood samples were collected at treatment and at days 1, 2, 3, 6, 9 and 16 post treatment. Plasma concentrations of ivermectin were determined by high-pressure liquid chromatography (HPLC) with fluorescence detection.

Results

The peak plasma concentration (C_max) was reached by 2 days after each treatment. The C_max and Area Under Curve (AUC) differed significantly between the groups: C_max was 30.2 ± 3.9, 14.9 ± 5.7 and 63.1 ± 13.1 ng/ml, and AUC_∞ was 2881 ± 462, 1299 ± 342 and 6718 ± 1620 ng*h/ml for groups 1, 2 and 3, respectively (mean ± standard deviation).

Conclusions

The differences in plasma concentrations of ivermectin are concomitant with earlier observed differences in antiparasitic efficacy, which discounts the use of the equine paste in reindeer in favour of the oral ovine liquid drench formulation, or preferably, the reindeer-registered subcutaneous injection formulation.     

Levetiracetam Rectal Administration in Healthy Dogs

Background

Levetiracetam is used to manage status epilepticus (SE) and cluster seizures (CS) in humans. The drug might be absorbed after rectal administration and could offer a practical adjunct to rectal administration of diazepam in managing SE and CS.

Hypothesis

Levetiracetam is rapidly absorbed after rectal administration in dogs and maintains target serum concentrations for at least 9 hours.

Animals

Six healthy privately owned dogs between 2 and 6 years of age and weighing 10–20 kg.

Methods

Levetiracetam (40 mg/kg) was administered rectally and blood samples were obtained immediately before (time zero) and at 10, 20, 40, 60, 90, 180, 360, and 540 minutes after drug administration. Dogs were observed for signs of adverse effects over a 24‐hour period after drug administration.

Results

C _LEV at 10 minutes was 15.3 ± 5.5 μg/mL (mean, SD) with concentrations in the target range (5–40 μg/mL) for all dogs throughout the sampling period. C _max (36.0 ± 10.7 μg/mL) and T _max (103 ± 31 minutes) values were calculated and 2 disparate groups were appreciated. Dogs with feces in the rectum at the time of drug administration had lower mean C _max values (26.7 ± 3.4 μg/mL) compared with those without (45.2 ± 4.4 μg/mL). Mild sedation was observed between 60 and 90 minutes without other adverse effects noted.

Conclusions and Clinical Importance

This study supports the use of rectally administered levetiracetam in future studies of clinical effectiveness in the management of epileptic dogs.     

Evaluation of route and frequency of administration of three antimicrobial drugs in cattle

This study in six cows compared serum concentrations of trimethoprim and sulphadoxine (16 mg/kg body weight (BW)) after once daily and twice daily administration, and of procaine penicillin G (20,000 IU/kg BW) after subcutaneous (SQ) and intramuscular (IM) administration, and evaluated postmortem tissue concentrations of penicillin following SQ treatment. Trimethoprim and penicillin were measured microbiologically, and sulphadoxine colorimetrically. Using minimum inhibitory concentrations (MIC), trimethoprim reached serum concentrations above 0.5 μg/mL from 15 minutes to 120 minutes, and sulphadoxine exceeded 9.5 μg/mL from 10 minutes to 12 hours, after administration. At 24 hours after treatment, both had declined to below the MIC of most organisms. A second treatment at 12 hours maintained concentrations of sulphadoxine above 9.5 μg/mL for a further 24 hours. For penicillin administered IM and SQ, concentrations that peaked at 0.88 μg/mL would inhibit most common grampositive bacteria for the entire 24 hour period and fastidious gram-negative organisms from 90 minutes to 12 hours after SQ treatment, but for virtually the entire period after IM administration. Mean ± SD concentrations (μg/mL) of penicillin at euthanasia, five days after the last SQ administration, were 1.15 ± 1.27 (injection site), 1.00 ± 0.80 (liver), 0.90 ± 0.58 (renal cortex), 0,58 ± 0.17 (renal medulla), 0.13 ± 0.11 (diaphragm), 0.10 ± 0.08 (gluteal muscle), and 0.06 ± 0.04 (fat). Therefore, except for the most sensitive organisms, twice daily injection of trimethoprim/sulphadoxine (16 mg/kg BW) may be required. Penicillin G administered SQ at 20,000 IU/kg BW should provide effective serum levels for as long as IM administration against gram-positive organisms, but for only about half as long against gram-negative bacteria. The label withdrawal time of five days cannot be used when penicillin is given SQ at 20,000 IU/kg BW for three days.     

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.     

The Concentrations of Molybdenum and Zinc in Liver in Relation to Copper Accumulation in Normal and Copper Poisoned Sheep

The concentrations of copper, molybdenum and zinc were measured in the liver of normal grazing sheep and lambs from Eastern Norway, and in sheep dead of chronic copper poisoning. The following mean values were found: Normal sheep: 173 ± 130 μg Gu/g wet weight, 1.0 ±0.3 μg Mo/g, and 49 ± 10 μg Zn/g; lambs: 129 ± 59 μg Gu/g, 0.9 ± 0.3 μg Mo/g, and 46 ±9 μg Zn/g; sheep dead of copper poisoning: 429 ± 249 μg Gu/g, 0.4 ± 0.1 μg Mo/g, and 43 ± 2d μg Zn/g. Sheep with low liver copper (Gu < 10 μg/g) were also analyzed for molybdenum and zinc, with the following results: 1.0 ± 0.2 μg Mo/g, and 45 ± 8 μg Zn/g wet weight. The differences in liver copper between all the groups, and the differences in molybdenum concentrations between the normal sheep and the lambs and between the normal sheep and the poisoned sheep were significant (P < 0.001). No significant correlations between liver copper/liver molybdenum or liver copper/liver zinc were detected.     

Clinical pharmacokinetics of norfloxacin-glycine acetate after intravenous and oral administration in pigs

The pharmacokinetics and dosage regimen of norfloxacin-glycine acetate (NFLXGA) was investigated in pigs after a single intravenous (i.v.) or oral (p.o.) administration at a dosage of 7.2 mg/kg body weight. After both i.v. and p.o. administration, plasma drug concentrations were best fitted to an open two-compartment model with a rapid distribution phase. After i.v. administration of NFLXGA, the distribution (t_1/2α) and elimination half-life (t_1/2β) were 0.36 ± 0.07 h and 7.42 ± 3.55 h, respectively. The volume of distribution of NFLXGA at steady state (Vd_ss) was 4.66 ± 1.39 l/kg. After p.o. administration of NFLXGA, the maximal absorption concentration (C_max) was 0.43 ± 0.06 µg/ml at 1.36 ± 0.39 h (T_max). The mean absorption (t_1/2ka) and elimination half-life (t_1/2β) of NFLXGA were 0.78 ± 0.27 h and 7.13 ± 1.41 h, respectively. The mean systemic bioavailability (F) after p.o. administration was 31.10 ± 15.16%. We suggest that the optimal dosage calculated from the pharmacokinetic parameters is 5.01 mg/kg per day i.v. or 16.12 mg/kg per day p.o.     

Formulation of a rational dosage regimen of ceftiofur hydrochloride oily suspension by pharmacokinetic-pharmacodynamic (PK-PD) model for treatment of swine Streptococcus suis infection

BackgroundOur previously prepared ceftiofur (CEF) hydrochloride oily suspension shows potential wide applications for controlling swine Streptococcus suis infections, while the irrational dose has not been formulated.ObjectivesThe rational dose regimens of CEF oily suspension against S. suis were systematically studied using a pharmacokinetic-pharmacodynamic model method.MethodsThe healthy and infected pigs were intramuscularly administered CEF hydrochloride oily suspension at a single dose of 5 mg/kg, and then the plasma and pulmonary epithelial lining fluid (PELF) were collected at different times. The minimum inhibitory concentration (MIC), minimal bactericidal concentration, mutant prevention concentration (MPC), post-antibiotic effect (PAE), and time-killing curves were determined. Subsequently, the area under the curve by the MIC (AUC_0–24h/MIC) values of desfuroylceftiofur (DFC) in the PELF was obtained by integrating in vivo pharmacokinetic data of the infected pigs and ex vivo pharmacodynamic data using the sigmoid E_max (Hill) equation. The dose was calculated based on the AUC_0–24h/MIC values for bacteriostatic action, bactericidal action, and bacterial elimination.ResultsThe peak concentration, the area under the concentration-time curve, and the time to peak for PELF''s DFC were 24.76 ± 0.92 µg/mL, 811.99 ± 54.70 μg·h/mL, and 8.00 h in healthy pigs, and 33.04 ± 0.99 µg/mL, 735.85 ± 26.20 μg·h/mL, and 8.00 h in infected pigs, respectively. The MIC of PELF''s DFC against S. suis strain was 0.25 µg/mL. There was strong concentration-dependent activity as determined by MPC, PAE, and the time-killing curves. The AUC_0–24h/MIC values of PELF''s DFC for bacteriostatic activity, bactericidal activity, and virtual eradication of bacteria were 6.54 h, 9.69 h, and 11.49 h, respectively. Thus, a dosage regimen of 1.94 mg/kg every 72 h could be sufficient to reach bactericidal activity.ConclusionsA rational dosage regimen was recommended, and it could assist in increasing the treatment effectiveness of CEF hydrochloride oily suspension against S. Suis infections.     

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 Total Thyroxine after Repeated Oral Administration of Levothyroxine Solution and its Clinical Efficacy in Hypothyroid Dogs

Background

Oral levothyroxine (l‐T₄) supplementation is commonly used to treat hypothyroid dogs.

Objectives

Investigate the plasma profile and pharmacokinetics of total thyroxine (tT₄) after PO administration of a l‐T₄ solution and its clinical efficacy in hypothyroid dogs.

Animals

Ten dogs with naturally occurring hypothyroidism.

Methods

After hypothyroidism diagnosis and supplementation with l‐T₄ solution PO q24h at 20 μg/kg BW for minimum 4 weeks, the plasma profile and pharmacokinetics of tT₄ were determined over 34 hours and the clinical condition of the dogs was evaluated.

Results

Before dosing for pharmacokinetic evaluation, mean tT₄ concentration was 23 ± 9 nmol/L. l‐T₄ was absorbed rapidly (t _max, 5 hours), reaching a mean maximal tT₄ concentration of 56 ± 11 nmol/L. The apparent terminal half‐life was 11.8 hours. Clinical signs of hypothyroidism improved or resolved in all dogs after 4 weeks of treatment. The dosage of 20 μg/kg PO q24h was judged appropriate in 5 dogs, and 4 dogs required slight increases (9–16%). Twice daily treatment, with a 30% increase in dosage, was necessary for 1 dog.

Conclusions and Clinical Importance

The pharmacokinetics of l‐T₄ in hypothyroid dogs was similar to that reported in healthy euthyroid dogs. Clinical and hormonal responses to l‐T₄ solution were rapid in all dogs. The starting dosage of 20 μg/kg PO q24h was suitable for maintenance supplementation in 50% of the dogs, minor dosage modification was required in 4 other dogs, and treatment q12h was required in 1 dog.     

The interaction of nitrous oxide and fentanyl on the minimum alveolar concentration of sevoflurane blocking motor movement (MACNM) in dogs

The study objective was to determine the effects of 70% nitrous oxide (N₂O) and fentanyl on the end-tidal concentration of sevoflurane necessary to prevent movement (MAC_NM) in response to noxious stimulation in dogs. Six healthy, adult, intact male, mixed-breed dogs were used on 3 occasions in a randomized crossover design. After induction of anesthesia with sevoflurane, each of the following treatments was randomly administered: fentanyl loading dose (Ld) of 15 μg/kg and infusion of 6 μg/kg per hour [treatment 1 (T1)], 70% N₂O (T2), or fentanyl (Ld of 15 μg/kg and infusion of 6 μg/kg per hour) combined with 70% N₂O (T3). Each dog received each of the 3 treatments once during the 3-week period. Determination of MAC_NM was initiated 90 min after the start of each treatment. The values were compared using the baseline MAC_NM, which had been determined in a previous study on the same group of dogs. Data were analyzed using a mixed-model analysis of variance (ANOVA) and Tukey-Kramer tests, and expressed as least squares mean ± SEM. The baseline MAC_NM decreased by 36.6 ± 4.0%, 15.0 ± 4.0%, and 46.0 ± 4.0% for T1, T2, and T3, respectively (P < 0.05), and differed (P < 0.05) among treatments. Mean fentanyl plasma concentrations did not differ (P ≥ 0.05) between T1 (3.70 ± 0.56 ng/mL) and T3 (3.50 ± 0.56 ng/mL). The combination of fentanyl and N₂O resulted in a greater sevoflurane MAC_NM sparing effect than either treatment alone.     

Pharmacokinetics of thymoquinone in layer chickens following oral and intravenous administration

Thymoquinone (TQ) is the major constituent of Nigella sativa and known to possess a variety of pharmacological effects. This study was designed to evaluate the pharmacokinetic profile of TQ following oral (PO) and intravenous (IV) administration in layer chickens. The layer chickens were equally divided into two groups (six chickens in each group, total 12 chickens), and TQ was administered via PO and IV routes. For PO route, the dose was 20 mg/kg b.w. and for IV route, 5 mg/kg b.w. was administered, respectively. A sensitive and accurate High‐Performance Liquid Chromatography (HPLC) technique was validated for the quantification of TQ from plasma. The limit of detection (LOD) and limit of quantification (LOQ) were 0.02 µg/ml and 0.05 µg/ml, respectively with >80% recovery. Maximum plasma concentration (C_max) following PO and IV administration was 8.805 and 4.497 µg/ml, respectively, while time to reach at maximum concentration (T_max) was 1 and 0.1 hr, respectively. The elimination half‐lives were recorded as 1.02 and 0.978 hr, whereas the mean residence times were 1.79 and 1.036 hr following both PO and IV administration, respectively. The 85% PO bioavailability was indicative that TQ could be used for various therapeutic purposes in layer chickens.     

The anesthetic interaction of propofol and sevoflurane on the minimum alveolar concentration preventing motor movement (MACNM) in dogs

The objective of this study was to determine the effects of propofol on the minimum alveolar concentration of sevoflurane needed to prevent motor movement (MAC_NM) in dogs subjected to a noxious stimulus using randomized crossover design. Six, healthy, adult beagles (9.2 ± 1.3 kg) were used. Dogs were anesthetized with sevoflurane on 3 occasions, at weekly intervals, and baseline MAC_NM (MAC_NM-B) was determined on each occasion. Propofol treatments were administered as loading dose (LD) and constant rate infusion (CRI) as follows: Treatment 1 (T1) was 2 mg/kg body weight (BW) and 4.5 mg/kg BW per hour; T2 was 4 mg/kg BW and 9 mg/kg BW per hour; T3 was 8 mg/kg BW and 18 mg/kg BW per hour, respectively. Treatment MAC_NM (MAC_NM-T) determination was initiated 60 min after the start of the CRI. Two venous blood samples were collected and combined at each MAC_NM-T determination for measurement of blood propofol concentration using high-performance liquid chromatography method (HPLC). Data were analyzed using a mixed-model ANOVA and are presented as least square means (LSM) ± standard error of means (SEM).Propofol infusions in the range of 4.5 to 18 mg/kg BW per hour resulted in mean blood concentrations between 1.3 and 4.4 μg/mL, and decreased (P < 0.05) sevoflurane MAC_NM in a concentration-dependent manner. The percentage decrease in MAC_NM was 20.5%, 43.0%, and 68.3%, with corresponding blood propofol concentrations of 1.3 ± 0.3 μg/mL, 2.5 ± 0.3 μg/mL, and 4.4 ± 0.3 μg/mL, for T1, T2, and T3, respectively. Venous blood propofol concentrations were strongly correlated (r = 0.855, P < 0.0001) with the decrease in MAC_NM. In dogs, propofol decreased the sevoflurane MAC_NM in a concentration-dependent manner.     

The Concentrations of Copper,Zinc and Molyrdenum in Swine Liver and the Relationship to the Distrirution of Solurle Copper- and Zinc-Rinding Proteins

The concentrations of copper, zinc and molybdenum were measured in liver samples from 21 normal slaughter pigs (average age about 6 months) and in 36 sows (average age about 2 years). The following mean values were found: Slaughter pigs: 15 ± 8 µg Cu/g, 45 ± 7 μg Zm/g and 1.0 ± 0.2 μg Mo/g wet weight; sows: 46 ± 70 μg Cu/g, 70 ± 26 μg Zn/g and 1.3 ± 0.3 μg Mo/g wet weight. The concentrations of all 3 elements were significantly higher in the sows than in the young pigs. There was no correlation between the concentrations of copper, zinc or molybdenum. The recorded copper levels in the slaughter pigs were in accordance with the levels of non-supplemented pigs given in the literature. The soluble hepatic copper- and zinc-binding proteins were separated into 3 different fractions by gel filtration. With increasing copper and zinc levels in the liver, a higher relative amount of these elements were found in the low molecular weight fraction.     

Pharmacokinetics of extended-release ivermectin microspheres after oral administration to healthy pigs

We compared the pharmacokinetics of ivermectin premix and ivermectin microspheres in pigs after single and multiple administration regimes. In the single-dose experiments, 24 piglets were randomly divided into three groups and given ivermectin at 0.3 mg/kg using (a) 1.0% ivermectin administered subcutaneously, (b) 0.25% ivermectin premix orally, and (c) 0.25% ivermectin microspheres orally. In the multiple-dose experiment, 6 pigs in two equal groups received ivermectin premix and microspheres orally at 0.3 mg/kg for 7 consecutive days to monitor the valley plasma levels. The plasma samples were detected by fluorescence high-performance liquid chromatography, and concentration–time data were fitted to a noncompartmental model. After oral administration of ivermectin microspheres at a single dose, the elimination rate constant (Kel), the half-life (t_1/2), the peak time (T_max), the mean residence time (MRT), and the peak concentration (C_max) were 0.012 ± 0.0031/hr, 59.94 ± 20.18 hr, 9.50 ± 0.93 hr, 55.96 ± 11.40 hr, and 37.75 ± 3.45 ng/ml, respectively. The C_max of microspheres was not statistically different (p > .05) compared with that of premix groups (39.81 ± 5.83 ng/ml). Moreover, the AUC of the microcapsule groups was increased from 1,129.76 ± 245.62 to 1,607.33 ± 343.35 hr ng/ml compared with the premix groups, and the relative bioavailability increased by an average of 17.53% after oral administration with ivermectin microspheres. Multiple-dose administration also indicated pigs fed with ivermectin microspheres can get a higher minimum steady-state concentration and a longer maintenance time than ivermectin premix.     

Preparation and evaluation of enrofloxacin microspheres and tissue distribution in rats

New enrofloxacin microspheres were formulated, and their physical properties, lung-targeting ability, and tissue distribution in rats were examined. The microspheres had a regular and round shape. The mean diameter was 10.06 µm, and the diameter of 89.93% of all microspheres ranged from 7.0 µm to 30.0 µm. Tissue distribution of the microspheres was evaluated along with a conventional enrofloxacin preparation after a single intravenous injection (7.5 mg of enrofloxacin/kg bw). The results showed that the elimination half-life (t_1/2β) of enrofloxacin from lung was prolonged from 7.94 h for the conventional enrofloxacin to 13.28 h for the microspheres. Area under the lung concentration versus time curve from 0 h to ∞ (AUC_0-∞) was increased from 11.66 h·µg/g to 508.00 h·µg/g. The peak concentration (C_max) in lung was increased from 5.95 µg/g to 93.36 µg/g. Three lung-targeting parameters were further assessed and showed that the microspheres had remarkable lung-targeting capabilities.     

Effect of ketoprofen co-administration on pharmacokinetics of cefquinome following repeated administration in goats

The pharmacokinetics of cefquinome (2 mg/kg every 24 hr for 5 days) was determined following intramuscular administration alone and co-administration with ketoprofen (3 mg/kg every 24 hr for 5 days) in goats. Six goats were used for the study. In the study, the crossover pharmacokinetics design with 20-day washout period was performed in two periods. Plasma concentrations of cefquinome were assayed using high-performance liquid chromatography by ultraviolet detection. The mean terminal elimination half-life (t_1/2ʎz), area under the concentration–time curve (AUC_0–24), peak concentration (C_max), apparent volume of distribution (V_darea/F), and total body clearance (CL/F) of cefquinome after the administration alone were 4.85 hr, 11.06 hr*µg/ml, 2.37 µg/mL, 1.23 L/kg, and 0.17 L/h/kg after the first dose, and 5.88 hr, 17.01 hr*µg/mL, 3.04 µg/mL, 0.95 L/kg, and 0.11 L/h/kg after the last dose. Ketoprofen significantly prolonged t_1/2ʎz of cefquinome, increased AUC_0–24 and C_max, and decreased V_darea/F and CL/F. Cefquinome exhibited low accumulation after the administration alone and in combination with ketoprofen. These results indicated that ketoprofen prolonged the elimination of cefquinome in goats. The 24-hr dosing intervals at 2 mg/kg dose of cefquinome, which co-administered with ketoprofen, may maintain T> minimum inhibitory concentration (MIC) values above 40% in the treatment of infections caused by susceptible pathogens with the MIC value of ≤0.75 μg/ml in goats with an inflammatory condition.     

In vivo metabolism of Talosin A, new isoflavonol glycoside from Kitasatospora kifunensis, in rats

The isoflavonol glycoside Talosin A, genistein (GT)-7-α-L-6-deoxy talopyranose (GT-Tal), was first isolated from the culture broth of Kitasatospora kifunensis MJM341. The aim of the present study was to evaluate the oral absorption and metabolism of the newly isolated isoflavonol glycoside, GT-Tal compared to genistin (GT-7-O-β-D-glucopyranoside; GT-Glu). Free GT-Glu and GT-Tal could not be detected prior to enzymatic hydrolysis of the corresponding conjugates in rat plasma. Following oral administration of GT-Tal (15 min), GT-Tal was rapidly absorbed through the gastrointestinal tract and metabolized into GT-Tal conjugates with a mean C_max of 2.74 µg/mL. GT-Tal was further metabolized to its aglycone, free GT and conjugated GT. After oral administration, GT-Glu was absorbed after being convereted to its aglycone and then further metabolized into its conjugate metabolites (free GT with a mean C_max of 0.24 mg/mL at 1.25 h; conjugated GT with a mean C_max of 1.31 mg/mL at 2.00 h). Significant differences in absorption and metabolism of GT-Tal and GT-Glu were observed. GT-Tal was metabolized into its corresponding conjugates or underwent deglycosylation to form GT, whereas GT-Glu was metabolized into its aglycone, GT.     

Population pharmacokinetics of itraconazole solution after a single oral administration in captive lesser flamingos (Phoeniconaias minor)

Aspergillosis is an infectious, non‐contagious fungal disease of clinical importance in flamingo collections. Itraconazole is an antifungal drug commonly used in the treatment and prophylaxis of avian aspergillosis. Studies have shown that dosage regimes in birds vary based on different itraconazole presentation and administration methods. This investigation used a population pharmacokinetic approach to study itraconazole in lesser flamingos. Itraconazole was administered orally at 10 mg/kg to 17 flamingos. A sparse blood sampling was performed on the subjects, and samples were collected at 1, 2, 3, 5, 8, 12, 16, 21, and 24 hr post‐drug administration. Twelve flamingos were sampled three times, three birds bled twice and two sampled once. Itraconazole in plasma was quantified using high‐pressure liquid chromatography (HPLC). A one‐compartment pharmacokinetic model with first order absorption was fitted to the data using nonlinear mixed effects modeling (NLME) to determine values for population parameters. We identified a long half‐life (T½) of more than 75 hr and a maximum plasma concentration (C_MAX) of 1.69 µg/ml, which is above the minimal inhibitory concentrations for different aspergillus isolates. We concluded that plasma drug concentrations of itraconazole were maintained in a population of flamingos above 0.5 ug/ml for at least 24 hr after a single oral dose of 10 mg/kg of itraconazole solution.