Pharmacokinetics of oxymorphone in cats

Siao, K. T., Pypendop, B. H., Stanley, S. D., Ilkiw, J. E. Pharmacokinetics of oxymorphone in cats. J. vet. Pharmacol. Therap. 34 , 594–598. This study reports the pharmacokinetics of oxymorphone in spayed female cats after intravenous administration. Six healthy adult domestic shorthair spayed female cats were used. Oxymorphone (0.1 mg/kg) was administered intravenously as a bolus. Blood samples were collected immediately prior to oxymorphone administration and at various times up to 480 min following administration. Plasma oxymorphone concentrations were determined by liquid chromatography–mass spectrometry, and plasma oxymorphone concentration–time data were fitted to compartmental models. A three‐compartment model, with input in and elimination from the central compartment, best described the disposition of oxymorphone following intravenous administration. The apparent volume of distribution of the central compartment and apparent volume of distribution at steady state [mean ± SEM (range)] and the clearance and terminal half‐life [harmonic mean ± jackknife pseudo‐SD (range)] were 1.1 ± 0.2 (0.4–1.7) L/kg, 2.5 ± 0.4 (2.4–4.4) L/kg, 26 ± 7 (18–38) mL/min.kg, and 96 ± 49 (62–277) min, respectively. The disposition of oxymorphone in cats is characterized by a moderate volume of distribution and a short terminal half‐life.     

Pharmacokinetics of fentanyl,alfentanil, and sufentanil in isoflurane‐anesthetized cats

The aim of this study was to compare the pharmacokinetics of fentanyl, alfentanil, and sufentanil in isoflurane‐anesthetized cats. Six adult cats were used. Anesthesia was induced and maintained with isoflurane in oxygen. End‐tidal isoflurane concentration was set at 2% and adjusted as required due to spontaneous movement. Fentanyl (10 μg/kg), alfentanil (100 μg/kg), or sufentanil (1 μg/kg) was administered intravenously as a bolus, on separate days. Blood samples were collected immediately before and for 8 h following drug administration. Plasma drug concentration was determined using liquid chromatography/mass spectrometry. Compartment models were fitted to concentration–time data. A 3‐compartment model best fitted the concentration–time data for all drugs, except for 1 cat in the sufentanil group (excluded from analysis). The volume of the central compartment and the volume of distribution at steady‐state (L/kg) [mean ± SEM (range)], the clearance (mL/min/kg) [harmonic mean ± pseudo‐SD (range)], and the terminal half‐life (min) [median (range)] were 0.25 ± 0.04 (0.09–0.34), 2.18 ± 0.16 (1.79–2.83), 18.6 ± 5.0 (15–29.8), and 151 (115–211) for fentanyl; 0.10 ± 0.01 (0.07–0.14), 0.89 ± 0.16 (0.68–1.83), 11.6 ± 2.6 (9.2–15.8), and 144 (118–501) for alfentanil; and 0.06 ± 0.01 (0.04–0.10), 0.77 ± 0.07 (0.63–0.99), 17.6 ± 4.3 (13.9–24.3), and 54 (46–76) for sufentanil. Differences in clearance and volume of distribution result in similar terminal half‐lives for fentanyl and alfentanil, longer than for sufentanil.     

Pharmacokinetics of dexmedetomidine,MK‐467, and their combination following intravenous administration in male cats

This study characterized the pharmacokinetics of dexmedetomidine, MK‐467, and their combination following intravenous bolus administration to cats. Seven 6‐ to‐year‐old male neutered cats, weighting 5.1 ± 0.7 kg, were used in a randomized, crossover design. Dexmedetomidine [12.5 (D12.5) and 25 (D25) μg/kg], MK‐467 [300 μg/kg (M300)] or dexmedetomidine (25 μg/kg) and MK‐467 [75, 150, 300 or 600 μg/kg—only the plasma concentrations in the 600 μg/kg group (D25M600) were analyzed] were administered intravenously, and blood was collected until 8 hours thereafter. Plasma drug concentrations were analyzed using liquid chromatography/mass spectrometry. A two‐compartment model best fitted the data. Median (range) volume of the central compartment (mL/kg), volume of distribution at steady state (mL/kg), clearance (mL min/kg) and terminal half‐life (min) were 342 (131–660), 829 (496–1243), 14.6 (9.6–22.7) and 48 (40–69) for D12.5; 296 (179–982), 1111 (908–2175), 18.2 (12.4–22.9) and 52 (40–76) for D25; 653 (392–927), 1595 (1094–1887), 22.7 (18.5–36.4) and 48 (35–60) for dexmedetomidine in D25M600; 117 (112–163), 491 (379–604), 3.0 (2.0‐4.5) and 122 (99‐139) for M300; and 147 (112‐173), 462 (403‐714), 2.8 (2.1–4.8) and 118 (97–172) for MK‐467 in D25M600. MK‐467 moderately but statistically significantly affected the disposition of dexmedetomidine, whereas dexmedetomidine minimally affected the disposition of MK‐467.     

Pharmacokinetics of buprenorphine following intravenous and buccal administration in cats,and effects on thermal threshold

This study reports the pharmacokinetics of buprenorphine, following i.v. and buccal administration, and the relationship between buprenorphine concentration and its effect on thermal threshold. Buprenorphine (20 μg/kg) was administered intravenously or buccally to six cats. Thermal threshold was determined, and arterial blood sampled prior to, and at various times up to 24 h following drug administration. Plasma buprenorphine concentration was determined using liquid chromatography/mass spectrometry. Compartment models were fitted to the time–concentration data. Pharmacokinetic/pharmacodynamic models were fitted to the concentration‐thermal threshold data. Thermal threshold was significantly higher than baseline 44 min after buccal administration, and 7, 24, and 104 min after i.v. administration. A two‐ and three‐compartment model best fitted the data following buccal and i.v. administration, respectively. Following i.v. administration, mean ± SD volume of distribution at steady‐state (L/kg), clearance (mL·min/kg), and terminal half‐life (h) were 11.6 ± 8.5, 23.8 ± 3.5, and 9.8 ± 3.5. Following buccal administration, absorption half‐life was 23.7 ± 9.1 min, and terminal half‐life was 8.9 ± 4.9 h. An effect‐compartment model with a simple effect maximum model best predicted the time‐course of the effect of buprenorphine on thermal threshold. Median (range) k_e0 and EC50 were 0.003 (0.002–0.018)/min and 0.599 (0.073–1.628) ng/mL (i.v.), and 0.017 (0.002–0.023)/min and 0.429 (0.144–0.556) ng/mL (buccal).     

The pharmacokinetics of methocarbamol and guaifenesin after single intravenous and multiple‐dose oral administration of methocarbamol in the horse

A simple LC/MSMS method has been developed and fully validated to determine concentrations and characterize the concentration vs. time course of methocarbamol (MCBL) and guaifenesin (GGE) in plasma after a single intravenous dose and multiple oral dose administrations of MCBL to conditioned Thoroughbred horses. The plasma concentration–time profiles for MCBL after a single intravenous dose of 15 mg/kg of MCBL were best described by a three‐compartment model. Mean extrapolated peak (C₀) plasma concentrations were 23.2 (±5.93) μg/mL. Terminal half‐life, volume of distribution at steady‐state, mean residence time, and systemic clearance were characterized by a median (range) of 2.96 (2.46–4.71) h, 1.05 (0.943–1.21) L/kg, 1.98 (1.45–2.51) h, and 8.99 (6.68–10.8) mL/min/kg, respectively. Oral dose of MCBL was characterized by a median (range) terminal half‐life, mean transit time, mean absorption time, and apparent oral clearance of 2.89 (2.21–4.88) h, 2.67 (1.80–2.87) h, 0.410 (0.350–0.770) h, and 16.5 (13.0–20) mL/min/kg. Bioavailability of orally administered MCBL was characterized by a median (range) of 54.4 (43.2–72.8)%. Guaifenesin plasma concentrations were below the limit of detection in all samples collected after the single intravenous dose of MCBL whereas they were detected for up to 24 h after the last dose of the multiple‐dose oral regimen. This difference may be attributed to first‐pass metabolism of MCBL to GGE after oral administration and may provide a means of differentiating the two routes of administration.     

Pharmacokinetics of tramadol, and its metabolite O-desmethyl-tramadol, in cats

Tramadol is an analgesic agent and is used in dogs and cats. Tramadol exerts its action through interactions with opioid, serotonin and adrenergic receptors. The opioid effect of tramadol is believed to be, at least in part, related to its metabolite, O-desmethyl-tramadol. The pharmacokinetics of tramadol and O-desmethyl-tramadol were examined after intravenous (i.v.) and oral administration of tramadol to six cats. A two-compartment model (with first-order absorption in the central compartment for the oral administration) with elimination from the central compartment best described the disposition of tramadol in cats. After i.v. administration, the apparent volume of distribution of the central compartment, the apparent volume of distribution at steady-state, the clearance, and the terminal half-life (mean +/- SEM) were 1553+/-118 mL/kg, 3103+/-132 mL/kg, 20.8+/-3.2 mL/min/kg, and 134+/-18 min, respectively. Systemic availability and terminal half-life after oral administration were 93+/-7% and 204+/-8 min, respectively. O-desmethyl-tramadol rapidly appeared in plasma following tramadol administration and had terminal half-lives of 261+/-28 and 289+/-19 min after i.v. and oral tramadol administration, respectively. The rate of formation of O-desmethyl-tramadol estimated from a model including both tramadol and O-desmethyl-tramadol was 0.014+/-0.003/min and 0.004+/-0.0008/min after i.v. and oral tramadol administration, respectively.     

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.     

Pharmacokinetics of pioglitazone in lean and obese cats(1)

Clark, M. H., Hoenig, M., Ferguson, D. C., Dirikolu, L. Pharmacokinetics of pioglitazone in lean and obese cats. J. vet. Pharmacol. Therap.  35 , 428–436. Pioglitazone is a thiazolidinedione insulin sensitizer that has shown efficacy in Type 2 diabetes and nonalcoholic fatty liver disease in humans. It may be useful for treatment of similar conditions in cats. The purpose of this study was to investigate the pharmacokinetics of pioglitazone in lean and obese cats, to provide a foundation for assessment of its effects on insulin sensitivity and lipid metabolism. Pioglitazone was administered intravenously (median 0.2 mg/kg) or orally (3 mg/kg) to 6 healthy lean (3.96 ± 0.56 kg) and 6 obese (6.43 ± 0.48 kg) cats, in a two by two Latin Square design with a 4‐week washout period. Blood samples were collected over 24 h, and pioglitazone concentrations were measured via a validated high‐performance liquid chromatography assay. Pharmacokinetic parameters were determined using two‐compartmental analysis for IV data and noncompartmental analysis for oral data. After oral administration, mean bioavailability was 55%, t_1/2 was 3.5 h, T_max was 3.6 h, C_max was 2131 ng/mL, and AUC_0–∞ was 15 556 ng/mL·h. There were no statistically significant differences in pharmacokinetic parameters between lean and obese cats following either oral or intravenous administration. Systemic exposure to pioglitazone in cats after a 3 mg/kg oral dose approximates that observed in humans with therapeutic doses.     

Enantioselective pharmacokinetics of racemic carprofen in New Zealand white rabbits

The enantioselective pharmacokinetics of single dose (2 mg/kg) racemic carprofen (CPF) were evaluated in adult New Zealand white rabbits after intravenous (i.v.) and subcutaneous (s.c.) dose. Six rabbits were utilized in a two‐way randomized crossover study and serial blood samples were collected. Plasma CPF concentrations were determined by high‐performance liquid chromatography. After i.v. and s.c. racemic CPF administration, plasma concentration–time curves were best described by a two‐compartment open model and a one‐compartment model, respectively. The S(+) CPF enantiomer predominated in plasma following both routes of administration. Mean observed clearance of R(?)‐CPF (82.17 ± 13.70 mL/h·kg) was more rapid than for S(+)‐CPF (27.92 ± 7.07 mL/h·kg; P < 0.001). T_1/2λz was shorter for R(?)‐CPF than S(+)‐CPF after both i.v. (1.03 and 2.99 h, respectively) and s.c. (1.94 and 4.14 h, respectively) dosing. Mean AUC_0→∞ ratios for R(?):S(+)‐CPF were approximately 1:3 for both routes of administration. Mean residence time of R(?)‐CPF was shorter than of S(+)‐CPF (1.06 ± 0.29 h, 3.45 ± 0.50 h; P < 0.001) and R(?)‐ and S(+)‐CPF volumes of distribution at steady state were 85.00 ± 14.42 and 94.39 ± 18.66 mL/kg, respectively after i.v. administration. The mean s.c. bioavailability [F (%)] for both R(?)‐ and S(+)‐CPF was high, 94.4 ± 22.8 and 91.0 ± 35.7%, respectively.     

Pharmacokinetics and pharmacodynamics of dermorphin in the horse

Dermorphin is a μ‐opioid receptor‐binding peptide that causes both central and peripheral effects following intravenous administration to rats, dogs, and humans and has been identified in postrace horse samples. Ten horses were intravenously and/or intramuscularly administered dermorphin (9.3 ± 1.0 μg/kg), and plasma concentration vs. time data were evaluated using compartmental and noncompartmental analyses. Data from intravenous administrations fit a 2‐compartment model best with distribution and elimination half‐lives (harmonic mean ± pseudo SD) of 0.09 ± 0.02 and 0.76 ± 0.22 h, respectively. Data from intramuscular administrations fit a noncompartmental model best with a terminal elimination half‐life of 0.68 ± 0.24 (h). Bioavailability following intramuscular administration was variable (47–100%, n = 3). The percentage of dermorphin excreted in urine was 5.0 (3.7–10.6) %. Excitation accompanied by an increased heart rate followed intravenous administration only and subsided after 5 min. A plot of the mean change in heart rate vs. the plasma concentration of dermorphin fit a hyperbolic equation (simple Emax model), and an EC₅₀ of 21.1 ± 8.8 ng/mL was calculated. Dermorphin was detected in plasma for 12 h and in urine for 48 or 72 h following intravenous or intramuscular administration, respectively.     

Characterization of the pharmacokinetic disposition of levofloxacin in stallions after intravenous and intramuscular administration

The target of the present study was to investigate the plasma disposition kinetics of levofloxacin in stallions (n = 6) following a single intravenous (i.v.) bolus or intramuscular (i.m.) injection at a dose rate of 4 mg/kg bwt, using a two‐phase crossover design with 15 days as an interval period. Plasma samples were collected at appropriate times during a 48‐h administration interval, and were analyzed using a microbiological assay method. The plasma levofloxacin disposition was best fitted to a two‐compartment open model after i.v. dosing. The half‐lives of distribution and elimination were 0.21 ± 0.13 and 2.58 ± 0.51 h, respectively. The volume of distribution at steady‐state was 0.81 ± 0.26 L/kg, the total body clearance (Cl_tot) was 0.21 ± 0.18 L/h/kg, and the areas under the concentration–time curves (AUCs) were 18.79 ± 4.57 μg.h/mL. Following i.m. administration, the mean t_1/2el and AUC values were 2.94 ± 0.78 h and 17.21 ± 4.36 μg.h/mL. The bioavailability was high (91.76% ± 12.68%), with a peak plasma mean concentration (C_max) of 2.85 ± 0.89 μg/mL attained at 1.56 ± 0.71 h (T_max). The in vitro protein binding percentage was 27.84%. Calculation of efficacy predictors showed that levofloxacin might have a good therapeutic profile against Gram‐negative and Gram‐positive bacteria, with an MIC ≤ 0.1 μg/mL.     

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.     

The pharmacokinetics of glycopyrrolate in Standardbred horses

The disposition of plasma glycopyrrolate (GLY) is characterized by a three‐compartment pharmacokinetic model after a 1‐mg bolus intravenous dose to Standardbred horses. The median (range) plasma clearance (Clp), volume of distribution of the central compartment (V₁), volume of distribution at steady‐state (Vss), and area under the plasma concentration–time curve (AUC_0‐inf) were 16.7 (13.6–21.7) mL/min/kg, 0.167 (0.103–0.215) L/kg, 3.69 (0.640–38.73) L/kg, and 2.58 (2.28–2.88) ng*h/mL, respectively. Renal clearance of GLY was characterized by a median (range) of 2.65 (1.92–3.59) mL/min/kg and represented approximately 11.3–24.7% of the total plasma clearance. As a result of these studies, we conclude that the majority of GLY is cleared through hepatic mechanisms because of the limited extent of renal clearance of GLY and absence of plasma esterase activity on GLY metabolism. Although the disposition of GLY after intravenous administration to Standardbred horses was similar to that in Thoroughbred horses, differences in some pharmacokinetic parameter estimates were evident. Such differences could be attributed to breed differences or study conditions. The research could provide valuable data to support regulatory guidelines for GLY in Standardbred horses.     

DIURETIC RENAL SCINTIGRAPHY IN NORMAL CATS

The purpose of this study was to develop a protocol for diuretic renal scintigraphy (renography) in cats and describe normal findings. ^99mTc‐DTPA renal scintigraphy was performed twice in 10 healthy cats. Furosemide or saline were injected 4.5 min after radiopharmaceutical administration for the diuretic or control scan, respectively. A dynamic acquisition was performed for 8 min. The following parameters were evaluated: (1) global and individual glomerular filtration rate (GFR); (2) shape of the time–activity curve (TAC); (3) time of peak (TOP); (4) individual kidney excretion half‐time (T_1/2) of the radiopharmaceutical; (5) percentage of maximum activity measured at the end of the study. Global GFR in the control studies (2.79±0.83 ml/min/kg, mean±SD) did not differ significantly from the diuretic scans (2.34±0.51 ml/min/kg). The shape of most (16/20) TAC of diuretic renograms was similar to those of control renograms. The TOP of the diuretic renogram curves was 3.06±0.58 min, and did not differ from that of the control scans (3.01±0.61 min). T_1/2 of the diuretic renograms was significantly shorter (5.15±0.83 min) than that of the control renograms (6.31±1.50 min). A significantly lower percentage of maximum activity was present at the end of the study in diuretic renograms (median: 47.25%; range: 33.60–59.60%) compared with control renograms (63.40%; 30.00–69.40%). Diuretic renal scintigraphy is a noninvasive and fast procedure to perform in cats. The applicability of this technique needs to be investigated in patients with significantly impaired renal function and obstructive uropathies.     

Pharmacokinetics of deflazacort in rabbits after intravenous and oral administration and its interaction with erythromycin

The pharmacokinetic of deflazacort after intravenous and oral administration and the effect of erythromycin on the disposition of deflazacort in rabbits were investigated. A parallel study was carried out in twelve rabbits. The plasma concentration–time profiles of deflazacort were determined after intravenous and oral administration of single dosages of 5 mg/kg in the presence and absence (baseline) of multiple dose erythromycin regimens. Plasma concentrations of 21‐desacetyldeflazacort were determined by HPLC. Plasma concentration–time curves were analysed by compartmental pharmacokinetic and noncompartmental methods. The t_½λz values following intravenous and oral administration were 3.67 and 4.96 hr, respectively. The apparent volume of distribution at steady‐state (V_ss) was 4.08 ± 0.31 L/kg, this value indicates that deflazacort is widely distributed into the extravascular tissues. Moreover, bioavailability after oral administration of deflazacort (F = 87.48%) was high. Pharmacokinetic analysis after both routes of administration revealed a significant reduction in total body clearance, a significant increase in mean residence time, half‐life and plasma concentrations of the steroid in the presence of multiple dose erythromycin. The results indicated the influence of the erythromycin on deflazacort disposition, which is consistent with a pharmacokinetic‐type interaction in the elimination of the drug from the body. Moreover, this interaction should be considered to avoid adverse effects when using both drugs concomitantly.     

Population pharmacokinetic modelling and simulation of single and multiple dose administration of meloxicam in cats

Lehr, T., Narbe, R., Jöns, O., Kloft, C., Staab, A. Population pharmacokinetic modelling and simulation of single and multiple dose administration of meloxicam in cats. J. vet. Pharmacol. Therap. 33 , 277–286. The objectives of these investigations were: first, to describe the pharmacokinetic properties of meloxicam in cats following single and multiple oral administration and secondly, to simulate different oral dosage regimes for meloxicam in cats after multiple dose administration to illustrate and evaluate those dosage regimes for the alleviation of inflammation and pain in cats. Six healthy domestic short hair cats were treated orally with various dosage regimes (0.05–0.2 mg/kg/day). Plasma samples were collected at predefined times and quantitatively analysed using liquid/liquid extraction followed by reverse phase HPLC with UV‐detection. Meloxicam plasma concentration data were analysed using the population pharmacokinetic approach (software: NONMEM). The final model was used to simulate different dosage regimes. The plasma concentration–time profiles of meloxicam in cats after oral single and multiple dose administration were best described by an open one‐compartment model with first‐order absorption and first‐order elimination. Pharmacokinetic parameters were estimated to be 0.00656 L/h/kg for the total apparent body clearance (CL/F), 0.245 L/kg for the apparent volume of distribution (V/F), 1.26 1/h for the absorption constant (K_A) and 25.7 h for the mean plasma terminal half‐life. Simulations showed that the median trough steady‐state concentrations of 228 ng/mL were reached after five, one or 6 days following a single initial dose of 0.05, 0.1 and 0.2 mg/kg each followed by 0.05 mg/kg/day.     

Bayesian population pharmacokinetic modeling of florfenicol in pigs after intravenous and intramuscular administration

Bayesian population pharmacokinetic models of florfenicol in healthy pigs were developed based on retrospective data in pigs either via intravenous (i.v.) or intramuscular (i.m.) administration. Following i.v. administration, the disposition of florfenicol was best described by a two‐compartment open model with the typical values of half‐life at α phase (t _1/2α), half‐life at β phase (t _1/2β), total body clearance (Cl), and volume of distribution (V _d) were 0.132 ± 0.0289, 2.78 ± 0.166 hr, 0.215 ± 0.0102, and 0.841 ± 0.0289 L kg^?1, respectively. The disposition of florfenicol after i.m. administration was best described by a one‐compartment open model. The typical values of maximum concentration of drug in serum (C _max), elimination half‐life (t _1/2Kel), Cl, and Volume (V ) were 5.52 ± 0.605 μg/ml, 9.96 ± 1.12 hr, 0.228 ± 0.0154 L hr^?1 kg^?1, and 3.28 ± 0.402 L/kg, respectively. The between‐subject variabilities of all the parameters after i.m. administration were between 25.1%–92.1%. Florfenicol was well absorbed (94.1%) after i.m. administration. According to Monte Carlo simulation, 8.5 and 6 mg/kg were adequate to exert 90% bactericidal effect against Actinobacillus pleuropneumoniae after i.v. and i.m. 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 C_MAX 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 oral rufinamide in dogs

Wright, H. M., Chen, A. V., Martinez, S. E., Davies, N. M. Pharmacokinetics of oral rufinamide in dogs. J. vet. Pharmacol. Therap.  35 , 529–533. The objective of this study was to determine the pharmacokinetic properties and short‐term adverse effect profile of single‐dose oral rufinamide in healthy dogs. Six healthy adult dogs were included in the study. The pharmacokinetics of rufinamide were calculated following administration of a single mean oral dose of 20.0 mg/kg (range 18.6–20.8 mg/kg). Plasma rufinamide concentrations were determined using high‐performance liquid chromatography, and pharmacokinetic data were analyzed using commercial software. No adverse effects were observed. The mean terminal half‐life was 9.86 ± 4.77 h. The mean maximum plasma concentration was 19.6 ± 5.8 μg/mL, and the mean time to maximum plasma concentration was 9.33 ± 4.68 h. Mean clearance was 1.45 ± 0.70 L/h. The area under the curve (to infinity) was 411 ± 176 μg·h/mL. Results of this study suggest that rufinamide given orally at 20 mg/kg every 12 h in healthy dogs should result in a plasma concentration and half‐life sufficient to achieve the therapeutic level extrapolated from humans without short‐term adverse effects. Further investigation into the efficacy and long‐term safety of rufinamide in the treatment of canine epilepsy is warranted.     

Pharmacokinetics of ganciclovir and valganciclovir in the adult horse

Equine herpes myeloencephalopathy, resulting from equine herpes virus type 1 (EHV‐1) infection, is associated with substantial morbidity and mortality in the horse. As compared to other antiviral drugs, such as acyclovir, ganciclovir has enhanced potency against EHV‐1. This study investigated the pharmacokinetics of ganciclovir and its oral prodrug, valganciclovir, in six adult horses in a randomized cross‐over design. Ganciclovir sodium was administered intravenously as a slow bolus at a dose of 2.5 mg/kg, and valganciclovir was administered orally at a dose of 1800 mg per horse. Intravenously administered ganciclovir disposition was best described by a three‐compartment model with a prolonged terminal half‐life of 72 ± 9 h. Following the oral administration of valganciclovir, the mean observed maximum serum ganciclovir concentration was 0.58 ± 0.37 μg/mL, and bioavailability of ganciclovir from oral valganciclovir was 41 ± 20%. Superposition predicted that oral dosing of 1800‐mg valganciclovir two times daily would fail to produce and maintain effective plasma concentrations of ganciclovir. However, superposition suggested that i.v. administration of ganciclovir at 2.5 mg/kg every 8 h for 24 h followed by maintenance dosing of 2.5 mg/kg every 12 h would maintain effective ganciclovir serum concentrations in most horses throughout the dosing interval.