Two doses of subcutaneous methadone for postoperative analgesia in dogs undergoing tibial plateau levelling osteotomies.

OBJECTIVES: To evaluate analgesia, sedation and adverse effects of two doses of subcutaneous methadone in dogs undergoing tibial plateau levelling osteotomy. MATERIALS AND METHODS: Seventeen client-owned dogs undergoing unilateral tibial plateau levelling osteotomy were randomly allocated to receive either 0.25 mg/kg methadone (eight dogs) or 0.5 mg/kg methadone (nine dogs). All dogs were premedicated with methadone and 2 to 6 mcg/kg dexmedetomidine subcutaneously. They were induced and maintained on a standard protocol. All animals received a second dose of methadone subcutaneously 4 hours after premedication and a 4.4 mg/kg dose of carprofen subcutaneously at 8 hours after premedication. During surgery, blood pressure, heart rate and temperature were assessed every 5 minutes. Postoperatively, sedation scores, temperature, heart rate and Glasgow composite modified pain score - short form were assessed for 12 hours postoperatively. RESULTS: One of 17 (5.9%) dogs had intraoperative hypotension, nine of 17 dogs had intra-operative bradyarrhythmias and 17 of 17 dogs had intra-operative hypothermia. No dogs required intra-operative rescue. Composite modified pain score - short form scores were below the threshold for intervention in 16 of 17 (94.1%) animals. Only one of 17 (5.9%) dogs required rescue analgesia. Median sedation score was 0 by the T8 time point. Adverse events were rare in both groups with only vocalisation and hypothermia reported commonly postoperatively. CLINICAL SIGNIFICANCE: Two doses of methadone at either 0.25 or 0.5 mg/kg administered via subcutaneous injections pre-operatively and 4 hours later, along with 4.4 mg/kg carprofen subcutaneously 8 hours after the first methadone dose appear to provide sufficient pain control for up to 12 hours in dogs undergoing tibial plateau levelling osteotomy.

Pharmacokinetics of oral tapentadol in cats.

To evaluate pharmacokinetics of one dose of tapentadol hydrochloride orally administered to cats. Prospective experimental study. Five healthy adult mixed-breed cats. Each cat received 18.8 ± 1.0 mg/kg tapentadol orally. Venous blood samples were collected at time 0 (immediately prior to administration of tapentadol) 1, 2, 5, 10, 15, 30, 45, 60, 90 min, and 2, 4, 8, 12 to 24 h after drug administration. Plasma tapentadol concentrations and its metabolites were determined using ultra-performance liquid chromatography-tandem mass spectrometry. Geometric mean Tmax of tapentadol, desmethyltapentadol, tapentadol-O-glucuronide, and tapentadol-O-sulfate was 2.3, 7.0, 6.0, and 4.6 h, respectively. Mean Cmax of tapentadol, desmethyltapentadol, tapentadol-O-glucuronide, and tapentadol-O-sulfate was 637, 66, 1134, and 15,757 ng/mL, respectively, after administration. Mean half-life of tapentadol, desmethyltapentadol, tapentadol-O-glucuronide, and tapentadol-O-sulfate was 2.4, 4.7, 2.9, and 10.8 h. The relative exposure of tapentadol and its metabolites were tapentadol 2.65%, desmethyltapentadol 0.54%, tapentadol-O-glucuronide 6.22%, and tapentadol-O-sulfate 90.6%. Tapentadol-O-sulfate was the predominant metabolite following the administration of oral tapentadol in cats. Further studies are warranted to evaluate the association of analgesia with plasma concentrations of tapentadol.

Pharmacokinetic evaluation of a sustained-release compounded procainamide preparation after 24-h (acute) administration in normal dogs.

INTRODUCTION: The objective of the present study was to evaluate the pharmacokinetics of a compounded sustained-release procainamide formulation in normal dogs. ANIMALS: Six healthy, purpose-bred mixed-breed dogs participated in the study. METHODS: In phase I, two dogs were administered oral procainamide (30 mg/kg), and plasma was obtained to determine plasma concentration ranges and duration. In phase II, six dogs were administered procainamide (30 mg/kg by mouth every 12 hours) to determine the pharmacokinetics of sustained-release procainamide. Serum procainamide concentration was determined using an immunochemistry assay. RESULTS: No adverse clinical effects were noted in any of the dogs studied. The average maximum serum concentration, average serum concentration, and average minimum serum concentration were 10.17, 7.13, and 3.07 µg/mL, respectively. The average time over a 12-h period during which procainamide concentration exceeded 12 µg/mL was 2.35 h, was between 4 and 12 µg/mL was 7.19 h, and was less than 4 µg/mL was 2.46 h. The average times at maximum concentration and minimum concentration were 18.67 and 12.25 h, respectively. CONCLUSIONS: Administration of sustained-release procainamide twice daily achieved targeted plasma concentrations in most dogs. Evaluation of serum trough concentrations should be considered owing to interanimal variability to confirm that serum concentrations are within the reported therapeutic range for an individual patient.

Bioavailability of suppository acetaminophen in healthy and hospitalized ill dogs.

To determine the plasma pharmacokinetics of suppository acetaminophen (APAP) in healthy dogs and clinically ill dogs. This prospective study used six healthy client-owned and 20 clinically ill hospitalized dogs. The healthy dogs were randomized by coin flip to receive APAP orally or as a suppository in crossover study design. Blood samples were collected up to 10 hr after APAP dosing. The hospitalized dogs were administered APAP as a suppository, and blood collected at 2 and 6 hr after dosing. Plasma samples were analyzed by ultra-performance liquid chromatography with triple quadrupole mass spectrometry. In healthy dogs, oral APAP maximal concentration (CMAX =2.69 µg/ml) was reached quickly (TMAX =1.04 hr) and eliminated rapidly (T1/2 = 1.81 hr). Suppository APAP was rapidly, but variably absorbed (CMAX =0.52 µg/ml TMAX =0.67 hr) and eliminated (T1/2  = 3.21 hr). The relative (to oral) fraction of the suppository dose absorbed was 30% (range <1%-67%). In hospitalized ill dogs, the suppository APAP mean plasma concentration at 2 hr and 6 hr was 1.317 µg/ml and 0.283 µg/ml. Nonlinear mixed-effects modeling did not identify significant covariates affecting variability and was similar to noncompartmental results. Results supported that oral and suppository acetaminophen in healthy and clinical dogs did not reach or sustain concentrations associated with efficacy. Further studies performed on different doses are needed.

The effects of ketoconazole and cimetidine on the pharmacokinetics of oral tramadol in greyhound dogs.

Tramadol is administered to dogs for analgesia but has variability in its extent of absorption, which may hinder its efficacy. Additionally, the active opioid metabolite (M1) occurs in low concentrations. The purpose of this study was to determine if administration of oral tramadol with suspected metabolism inhibitors (ketoconazole, cimetidine) would lead to improved bioavailability of tramadol and M1. Six healthy Greyhounds were included. They were administered tramadol orally and intravenously, M1 intravenously, oral tramadol with oral ketoconazole and oral tramadol with oral cimetidine. Oral tramadol bioavailability was low (2.6%). Ketoconazole and cimetidine significantly increased tramadol bioavailability to 18.2% and 20.3%, respectively. The mean maximum plasma concentration of tramadol alone was 22.9 ng/ml, and increased to 109.9 and 143.2 µg/ml with ketoconazole and cimetidine, respectively. However, measured tramadol plasma concentrations were below the minimum concentration considered effective in humans (228 µg/ml). In all treatment groups, measured M1 concentrations (<7 µg/ml) were below concentrations associated with efficacy in humans. To conclude, tramadol and M1 concentrations were low and variable in dogs after oral dosing of tramadol, even in combination with cimetidine or ketoconazole, but effective concentrations in dogs have not been defined.

Pharmacokinetics of oral terbinafine in adult horses.

The primary study objective was to compare the pharmacokinetics of p.o. terbinafine alone to p.o. terbinafine administered with p.o. cimetidine in healthy adult horses. The second objective was to assess the pharmacokinetics of terbinafine when administered per rectum in two different suspensions at 30 mg/kg to adult horses. Six healthy adult horses were included in this crossover study. Plasma terbinafine concentrations were quantified with liquid chromatography and mass spectrometry. The half-life (geometric mean) was 8.38 and 10.76 h, for p.o. alone and p.o. with cimetidine, respectively. The mean maximum plasma concentrations were 0.291 µg/mL at 1.54 h and 0.418 µg/mL at 1.28 h for p.o. alone and p.o. with cimetidine, respectively. Terbinafine with cimetidine had an average CMAX 44% higher and the relative F was 153% compared p.o. terbinafine alone, but was not statistically different (P > 0.05). Terbinafine was infrequently detected when administered per rectum in two different suspensions (water or olive oil). Minor adverse effects included oral irritation, fever, and colic. All resolved spontaneously. More pharmacokinetic studies are indicated assessing drug-drug interactions and using multiple dosing intervals to improve our knowledge of effective oral dosing, the potential for drug accumulation, and systemic adverse effect of terbinafine in horses.

The pharmacokinetics of transdermal flunixin meglumine in Holstein calves.

This study describes the pharmacokinetics of topical and intravenous (IV) flunixin meglumine in Holstein calves. Eight male Holsteins calves, aged 6 to 8 weeks, were administered flunixin at a dose of 2.2 mg/kg intravenously. Following a 10-day washout period, calves were dosed with flunixin at 3.33 mg/kg topically (transdermal). Blood samples were collected at predetermined times from 0 to 48 h for the intravenous portions and 0 to 72 h following topical dosing. Plasma drug concentrations were determined using liquid chromatography with mass spectroscopy. Pharmacokinetic analysis was completed using noncompartmental methods. The mean bioavailability of topical flunixin was calculated to be 48%. The mean AUC for flunixin was determined to be 13.9 h × ug/mL for IV administration and 10.1 h × ug/mL for topical administration. The mean half-life for topical flunixin was 6.42 h and 4.99 h for the intravenous route. The Cmax following topical application of flunixin was 1.17 µg/mL. The time to maximum concentration was 2.14 h. Mean residence time (MRT) following IV injection was 4.38 h and 8.36 h after topical administration. In conclusion, flunixin when administered as a topical preparation is rapidly absorbed and has longer half-life compared to IV administration.

Pharmacokinetics and pharmacodynamics of oral acetaminophen in combination with codeine in healthy Greyhound dogs.

The purpose of this study was to determine the pharmacokinetic and antinociceptive effects of an acetaminophen/codeine combination administered orally to six healthy greyhounds. Antinociception was assessed using an electronic von Frey (vF) device as a mechanical/pressure model. Acetaminophen was administered at a dose of 600 mg (14.4-23.1 mg/kg) and codeine phosphate at 90 mg (2.1-3.3 mg/kg) equivalent to 67.5 mg codeine base (1.6-2.5 mg/kg). The geometric mean maximum plasma concentrations of acetaminophen, codeine, and codeine-6-glucuronide were 7.95 µg/mL, 11.0 ng/mL, and 3819 ng/mL, respectively. Morphine concentrations were <1 ng/mL. The terminal half-lives of acetaminophen, codeine, and codeine-6-glucuronide were 0.94, 1.71, and 3.12 h. There were no significant changes in vF thresholds, except at 12 h which decreased on average by 17% compared to baseline. The decrease in vF thresholds at 12 h could be due to aversion, hyperalgesia, or random variability. The lack of antinociception in this study could be due to a true lack of antinociception, lack of model sensitivity, or specificity. Further studies using different models (including clinical trials), different dog breeds, multiple dose regimens, and a range of dosages are needed prior to recommended use or concluding lack of efficacy for oral acetaminophen/codeine in dogs.

Pharmacokinetics and pharmacodynamics of gamithromycin in pulmonary epithelial lining fluid in naturally occurring bovine respiratory disease in multisource commingled feedlot cattle.

The objectives of this study were to determine (i) whether an association exists between individual pharmacokinetic parameters and treatment outcome when feeder cattle were diagnosed with bovine respiratory disease (BRD) and treated with gamithromycin (Zactran(®) ) at the label dose and (ii) whether there was a stronger association between treatment outcome and gamithromycin concentration in plasma or in the pulmonary epithelial lining fluid (PELF) effect compartment. The study design was a prospective, blinded, randomized clinical trial utilizing three groups of 60 (362-592 lb) steers/bulls randomly allocated within origin to sham injection or gamithromycin mass medication. Cattle were evaluated daily for signs of BRD by a veterinarian blinded to treatment. Animals meeting the BRD case definition were enrolled and allocated to a sample collection scheme consisting of samples for bacterial isolation (bronchoalveolar lavage fluid and nasopharyngeal swabs) and gamithromycin concentration determination (PELF and plasma). Gamithromycin susceptibility of M. haemolytica (n = 287) and P. multocida (n = 257) were determined using broth microdilution with frozen panels containing gamithromycin at concentrations from 0.03 to 16 µg/mL. A two-compartment plasma pharmacokinetic model with an additional compartment for gamithromycin in PELF was developed using rich data sets from published and unpublished studies. The sparse data from our study were then fit to this model using nonlinear mixed effects modeling to estimate individual parameter values. The resulting parameter estimates were used to simulate full time-concentration profiles for each animal in this study. These profiles were analyzed using noncompartmental methods so that PK/PD indices (AUC24 /MIC, AUC∞ /MIC, CMAX /MIC) could be calculated for plasma and PELF (also T>MIC) for each individual. The calculated PK/PD indices were indicative that for both M. haemolytica and P. multocida a higher drug exposure in terms of concentration, and duration of exposure relative to the MIC of the target pathogen, was favorable to a successful case outcome. A significant association was found between treatment success and PELF AUC0-24 /MIC for P. multocida. The calves in this study demonstrated an increased clearance and volume of distribution in plasma as compared to the healthy calves in two previously published reports. Ultimately, the findings from this study indicate that higher PK/PD indices were predictive of positive treatment outcomes.

Altered plasma pharmacokinetics of ceftiofur hydrochloride in cows affected with severe clinical mastitis.

Mastitis is a frequent problem among dairy cows, reducing milk yield and increasing cull rates. Systemic therapy with the cephalosporin antimicrobial ceftiofur hydrochloride (CEF) may improve therapeutic outcomes, but the incidence of CEF violative residues has increased annually since 2011. One potential explanation is that disease status may alter the pharmacokinetics (PK) of CEF. To test this hypothesis, we compared the plasma PK of CEF in healthy cows with those with severe endotoxic mastitis. Eight cows with naturally occurring mastitis and 8 clinically healthy cows were treated with 2.2 mg of CEF per kilogram of body weight once daily for 5d via the intramuscular route. Blood was collected at 0, 0.33, 0.67, 1, 1.5, 2, 3, 4, 8, 16, and 24h after the first CEF administration and every 8h thereafter until 120 h after the final dose. Plasma samples were analyzed for CEF concentrations using liquid chromatography coupled with mass spectrometry. With the exception of time 0, CEF was detected at all time points. The disease group had a significantly higher plasma CEF concentration at t=3h after the first injection and a significantly lower plasma concentration from 40 to 152 h following the first injection, with the exception of the t=64 h time point. Data following the first injection (time 0-24 h) were fit to a single-dose, noncompartmental PK model. This model indicated that the disease group had a shorter plasma half-life. A multidose, noncompartmental model was used to determine steady-state PK. Compared with control cows, the disease group had an initially higher peak concentration and a higher volume of distribution and drug clearance rates. The disease group also had a lower area under the curve per dosing interval, steady-state concentration maximum, and dose-adjusted peak steady-state concentration. All other PK parameters were not different between the 2 groups. Altered PK, as suggested by this trial, may contribute to an increased risk for the development of a violative residue in meat. Further research is needed to more completely characterize drug distribution in diseased cattle and to study the effect of coadministration of other drugs on drug distribution.

Effect of Sucralfate on the Relative Bioavailability of Enrofloxacin and Ciprofloxacin in Healthy Fed Dogs.

BACKGROUND: Sucralfate impairs absorption of ciprofloxacin and other fluoroquinolones in humans, but no sucralfate-fluoroquinolone interaction has been reported in dogs. Veterinary formularies recommend avoiding concurrent administration of these medications, which might impact compliance, therapeutic success, and resistance selection from fluoroquinolones. OBJECTIVES: To determine whether a drug interaction exists when sucralfate is administered to fed dogs concurrently with ciprofloxacin or enrofloxacin, and whether a 2 hour delay between fluoroquinolone and sucralfate affects fluoroquinolone absorption. ANIMALS: Five healthy Greyhounds housed in a research colony. METHODS: This was a randomized crossover study. Treatments included oral ciprofloxacin (C) or oral enrofloxacin (E) alone, each fluoroquinolone concurrently with an oral suspension of sucralfate (CS, ES), and sucralfate suspension 2 hours after each fluoroquinolone (C2S, E2S). Fluoroquinolone concentrations were evaluated using liquid chromatography with mass spectrometry. RESULTS: Drug exposure of ciprofloxacin was highly variable (AUC 5.52-22.47 h µg/mL) compared to enrofloxacin (AUC 3.86-7.50 h µg/mL). The mean relative bioavailability for ciprofloxacin and concurrent sucralfate was 48% (range 8-143%) compared to ciprofloxacin alone. Relative bioavailability of ciprofloxacin improved to 87% (range 37-333%) when sucralfate was delayed by 2 hours. By contrast, relative bioavailability for enrofloxacin and concurrent sucralfate was 104% (94-115%). CONCLUSIONS AND CLINICAL IMPORTANCE: A possible clinically relevant drug interaction for the relative bioavailability of ciprofloxacin with sucralfate was found. No significant difference in bioavailability was documented for enrofloxacin with sucralfate. Further research is warranted in fasted dogs and clinical cases requiring enrofloxacin or other approved fluoroquinolones in combination with sucralfate.

Evaluation of the pharmacokinetics of oral amitriptyline and its active metabolite nortriptyline in fed and fasted Greyhound dogs.

This study reports the pharmacokinetics of oral amitriptyline and its active metabolite nortriptyline in Greyhound dogs. Five healthy Greyhound dogs were enrolled in a randomized crossover design. A single oral dose of amitriptyline hydrochloride (actual mean dose 8.1 per kg) was administered to fasted or fed dogs. Blood samples were collected at predetermined times from 0 to 24 h after administration, and plasma drug concentrations were measured by liquid chromatography with mass spectrometry. Noncompartmental pharmacokinetic analyses were performed. Two dogs in the fasted group vomited following amitriptyline administration and were excluded from analysis. The range of amitriptyline CMAX for the remaining fasted dogs (n = 3) was 22.8-64.5 ng/mL compared to 30.6-127 ng/mL for the fed dogs (n = 5). The range of the amitriptyline AUCINF for the three fasted dogs was 167-720 h·ng/mL compared to 287-1146 h·ng/mL for fed dogs. The relative bioavailability of amitriptyline in fasted dogs compared to fed dogs was 69-91% (n = 3). The exposure of the active metabolite nortriptyline was correlated to amitriptyline exposure (R(2)  = 0.84). Due to pharmacokinetic variability and the small number of dogs completing this study, further studies are needed assessing the impact of feeding on oral amitriptyline pharmacokinetics. Amitriptyline may be more likely to cause vomiting in fasted dogs.

Pharmacokinetics and tissue disposition of meloxicam in beef calves after repeated oral administration.

The objective of this study was to investigate the pharmacokinetics and tissue disposition of meloxicam after repeated oral administration in calves. Thirteen male British × Continental beef calves aged 4 to 6 months and weighing 297-392 kg received 0.5 mg/kg meloxicam per os once daily for 4 days. Plasma meloxicam concentrations were determined in 8 calves over 6 days after first treatment. Calves were randomly assigned to be euthanized at 5, 10, 15 (n = 3/timepoint), and 19 days (n = 4) after final administration. Meloxicam concentrations were determined in plasma (LOQ= 0.025 µg/mL) and muscle, liver, kidney, and fat samples (LOQ = 2 ng/g) after extraction using validated LC-MS-MS methods. The mean (± SD) Cmax , Cmin , and Caverage plasma meloxicam concentrations were 4.52 ± 0.87 µg/mL, 2.95 ± 0.77 µg/mL, and 3.84 ± 0.81 µg/mL, respectively. Mean (± SD) tissue meloxicam concentrations were highest in liver (226.67 ± 118.16 ng/g) and kidney samples (52.73 ± 39.01 ng/g) at 5 days after final treatment. Meloxicam concentrations were below the LOQ in all tissues at 15 days after treatment. These findings suggest that tissue from meloxicam-treated calves will have low residue concentrations by 21 days after repeated oral administration.

Pharmacokinetics of oral amantadine in greyhound dogs.

This study reports the pharmacokinetics of amantadine in greyhound dogs after oral administration. Five healthy greyhound dogs were used. A single oral dose of 100 mg amantadine hydrochloride (mean dose 2.8 mg/kg as amantadine hydrochloride) was administered to nonfasted subjects. Blood samples were collected at predetermined time points from 0 to 24 h after administration, and plasma concentrations of amantadine were measured by liquid chromatography with triple quadrupole mass spectrometry. Noncompartmental pharmacokinetic analyses were performed. Amantadine was well tolerated in all dogs with no adverse effects observed. The mean (range) amantadine CMAX was 275 ng/mL (225-351 ng/mL) at 2.6 h (1-4 h) with a terminal half-life of 4.96 h (4.11-6.59 h). The results of this study can be used to design dosages to assess multidose pharmacokinetics and dosages designed to achieve targeted concentrations in order to assess the clinical effects of amantadine in a variety of conditions including chronic pain. Further studies should also assess the pharmacokinetics of amantadine in other dog breeds or using population pharmacokinetics studies including multiple dog breeds to assess potential breed-specific differences in the pharmacokinetics of amantadine in dogs.

Pharmacokinetics of meloxicam in mature swine after intravenous and oral administration.

The purpose of this study was to compare the pharmacokinetics of meloxicam in mature swine after intravenous (i.v.) and oral (p.o.) administration. Six mature sows (mean bodyweight ± standard deviation = 217.3 ± 65.68 kg) were administered an i.v. or p.o. dose of meloxicam at a target dose of 0.5 mg/kg in a cross-over design. Plasma samples collected up to 48 h postadministration were analyzed by high-pressure liquid chromatography and mass spectrometry (HPLC-MS) followed by noncompartmental pharmacokinetic analysis. Mean peak plasma concentration (CMAX ) after p.o. administration was 1070 ng/mL (645-1749 ng/mL). TMAX was recorded at 2.40 h (0.50-12.00 h) after p.o. administration. Half-life (T½ λz ) for i.v. and p.o. administration was 6.15 h (4.39-7.79 h) and 6.83 h (5.18-9.63 h), respectively. The bioavailability (F) for p.o. administration was 87% (39-351%). The results of this study suggest that meloxicam is well absorbed after oral administration.

The effect of sucralfate tablets vs. suspension on oral doxycycline absorption in dogs.

The purpose of this study was to determine the effect of concurrent sucralfate (tablet or suspension) on doxycycline pharmacokinetics and to determine the effects of delaying sucralfate by 2 h on doxycycline absorption. Five dogs were included in a crossover study receiving: doxycycline alone; doxycycline concurrently with sucralfate tablet; doxycycline followed 2 h by sucralfate tablet; doxycycline concurrently with sucralfate suspension; and doxycycline followed 2 h by sucralfate suspension. Doxycycline plasma concentrations were evaluated with liquid chromatography with mass spectrometry. No interaction was seen when sucralfate was administered as a tablet. Sucralfate tablet fragments were frequently observed in some dogs' feces. The area under the curve (AUC) and maximum plasma concentration (CMAX ) were significantly lower (P < 0.001) in the concurrent sucralfate suspension group (AUC 7.2 h·µg/mL, CMAX 0.43 µg/mL) than with doxycycline alone (AUC 36.0 h·µg/mL, CMAX 2.53 µg/mL) resulting in a relative bioavailability of 20%. Delaying sucralfate suspension by 2 h after doxycycline administration resulted in no difference in doxycycline absorption as compared with doxycycline administration alone with a relative bioavailability of 74%. The lack of an interaction with sucralfate tablets suggests sucralfate should be administered as a suspension rather than tablet in dogs.

Comparative pharmacokinetics of intravenous fentanyl and buprenorphine in healthy greyhound dogs.

The purpose of this study was to compare the pharmacokinetics of two highly protein-bound, lipophilic opioid drugs. Fentanyl (10 µg/kg) and buprenorphine (20 µg/kg) were administered intravenously (IV) to six healthy greyhound dogs (three males and three females). The doses were based on clinically administered doses for dogs. Plasma drug concentrations were determined using liquid chromatography with mass spectrometry, and noncompartmental pharmacokinetics were estimated with computer software. The volume of distribution (area) was larger for fentanyl (7.42 L/kg) compared to buprenorphine (3.54 L/kg). The plasma clearance of fentanyl (38.6 mL·min/kg) was faster than buprenorphine (10.3 mL·min/kg). The terminal half-life of fentanyl (2.22 h) was shorter than buprenorphine (3.96 h). Despite similar physicochemical properties including octanol-water partition coefficient and pKa, the pharmacokinetics of fentanyl and buprenorphine were not similar. Both fentanyl (84%) and buprenorphine (95-98%) are considered highly protein bound, but the differences in protein binding may contribute to the lack of similarity of pharmacokinetics in healthy dogs.

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 (CMAX ) and area under the curve (AUC) of minocycline were 1.15 µg/mL and 8.0 h* µg/mL, respectively. The CMAX and AUC were significantly lower (P < 0.05) in the MS group (CMAX  = 0.33 µg/mL, AUC 3.0 h*µg/mL) compared with M or MS+2 (CMAX = 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).

Impact of oral meloxicam administered alone or in combination with gabapentin on experimentally induced lameness in beef calves.

This study examined the pharmacokinetics and analgesic effect of oral meloxicam (MEL) administered alone or in combination with gabapentin (GABA) in an experimental bovine lameness model. Eighteen male British × Continental beef calves aged 4 to 6 mo and weighing 297 to 392 kg were randomly assigned to receive either 1) 0.5 mg/kg lactose monohydrate placebo (PLBO; n = 6), 2) 0.5 mg/kg MEL (n = 6), or 3) 0.5 mg/kg MEL combined with 15 mg/kg GABA (MEL-GABA; n = 6) once daily for 4 d. The first treatment was administered 4 h after a chemical synovitis/arthritis was induced with injection of 15 mg amphotericin B into the left hind lateral distal interphalangeal joint. Changes in activity were evaluated continuously with pedometers. Contact force, contact area, contact pressure, impulse, and stride length were recorded once daily with a pressure mat and visual lameness scores were determined by a masked observer using a 5-point scale. Cortisol and drug concentrations were determined daily by immunoassay and HPLC-mass spectrometry, respectively. Outcomes were compared statistically using a random effects mixed model and analysis of covariance. There was a positive association between lameness scores and serum cortisol concentrations (P = 0.02) and a negative association between lameness score and step count (P < 0.0001), total force (P = 0.001), force applied to the lateral claw (P = 0.02), contact pressure (P = 0.005), and impulse of the lateral claw (P = 0.01). Step count was greater in MEL calves compared with PLBO (P = 0.008) and MEL-GABA (P = 0.04) calves. Impulse was greater in the MEL-GABA calves compared with the PLBO calves (P = 0.03). There was an inverse relationship between plasma MEL concentrations and lameness score (P = 0.02) and a positive association between MEL concentrations and force applied to the lateral claw (P = 0.03), total contact pressure (P = 0.03), and impulse on the lateral claw (P = 0.02). There was a tendency towards a positive association between GABA concentrations, total impulse, and impulse on the lateral claw (P = 0.08) and a negative associate between GABA concentrations and step count (P = 0.08). The results of this study suggest that MEL administered alone or in combination with GABA reduced the severity of lameness in calves following induction of lameness with amphotericin B. These findings have implications for developing analgesic protocols in lame calves that address both production and welfare concerns.