Pharmacokinetics of an ampicillin/sulbactam (2:1) combination in rabbits

The pharmacokinetics of a 2:1 ampicillin-sulbactam combination in six rabbits, after intravenous and intramuscular injection at a single dosage of 20 mg/kg bodyweight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam) were investigated by using a high performance liquid chromatographic method for determining plasma concentrations. The plasma concentration-time curves were analysed by compartmental pharmacokinetic and noncompartmental methods. The disposition curves for both drugs were best described by an open two-compartment model after intravenous administration and a one-compartment model with first order absorption after intramuscular administration. The apparent volumes of distribution calculated by the area method for ampicillin and sulbactam were 0.62 +/- 0.09 and 0.45 +/- 0.05 L/kg, respectively, and the total body clearances were 0.65 +/- 0.04 and 0.42 +/- 0.05 L/kg h, respectively. The elimination half-lives of ampicillin after intravenous and intramuscular administration were 0.64 +/- 0.11 and 0.63 +/- 0.16 h, respectively, whereas for sulbactam the half-lives were 0.74 +/- 0.12 and 0.77 +/- 0.17 h, respectively. The bioavailability after intramuscular injection was high and similar in both drugs (73.34 +/- 10.08% for ampicillin and 83.20 +/- 7.41% for sulbactam). The mean peak plasma concentrations of ampicillin and sulbactam were reached at similar times (0.20 +/- 0.09 and 0.34 +/- 0.15 h, respectively) and peak concentrations were also similar but nonproportional to the dose of both products administered (13.07 +/- 3.64 mg/L of ampicillin and 8.42 +/- 1.74 mg/L of sulbactam). Both drugs had similar pharmacokinetic behaviour after intramuscular administration in rabbits.     

Pharmacokinetics of an ampicillin-sulbactam combination after intravenous and intramuscular administration to sheep.

The pharmacokinetics of a 2:1 ampicillin-sulbactam combination were studied in 6 sheep, after intravenous and intramuscular injection at a single dose rate of 20 mg/kg body weight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam). The drugs were distributed according to an open 2-compartment model after intravenous administration and a one-compartment model with first order absorption after intramuscular administration. The apparent volumes of distribution calculated by the area method of ampicillin and sulbactam were 0.32+/-0.06 L/kg and 0.42+/-0.04 L/kg, respectively and the total body clearances were 0.69+/-0.07 and 0.38+/-0.03 L/kg x h, respectively. The elimination half-lives of ampicillin after intravenous and intramuscular administration were 0.32+/-0.05 h and 0.75+/-0.27 h, respectively, whereas for sulbactam the half-lives were 0.74+/-0.10 h and 0.89+/-0.16 h, respectively. The bioavailability after intramuscular injection was high and similar in both drugs (72.76+/-9.65% for ampicillin and 85.50+/-8.35% for sulbactam). The mean peak plasma concentrations of ampicillin and sulbactam were reached at similar times (0.25+/-0.10 h and 0.24+/-0.08 h, respectively) and peak concentrations were also similar but nonproportional to the dose of both products administered (13.01+/-7.36 mg/L of ampicillin and 10.39+/-3.95 mg/L of sulbactam). Both drugs had a similar pharmacokinetic behavior after intramuscular administration in sheep. Since the plasma concentrations of sulbactam where consistently higher during the elimination phase of their disposition, consideration could be given to formulating the ampicillin-sulbactam combination in a higher than 2:1 ratio.     

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

Summary

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

Pharmacokinetics of an ampicillin-sulbactam combination after intravenous and intramuscular administration to neonatal calves

The pharmacokinetics of a 2:1 ampicillin-sulbactam combination after intravenous (i.v.) and intramuscular (i.m.) injection at a single dose rate of 20 mg/kg bodyweight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam) were studied in 10-day-old neonatal calves (n = 10). The plasma concentration-time data of both antibiotics were best fitted to an open two-compartment model after i.v. administration. After i.m. administration, an open two-compartment model demonstrated first order absorption. The apparent volumes of distribution of ampicillin and sulbactam, calculated by the area method, were 0.20+/-0.01 and 0.18+/-0.01 L/kg, respectively, and the total body clearances were 0.51+/-0.03 and 0.21+/-0.01 L/kg h. The elimination half-lives of ampicillin after i.v. and i.m. administration were 0.99+/-0.03 and 1.01+/-0.02 h, respectively, whereas for sulbactam the half-lives were 2.24+/-0.02 and 3.44+/-0.94 h. The bioavailability after i.m. injection was high and similar for both drugs (70.31+/-0.2% for ampicillin and 68.62+/-4.44% for sulbactam). The mean peak plasma concentrations of ampicillin and sulbactam were reached at similar times (0.47+/-0.02 and 0.72+/-0.01 h, respectively) and peak concentrations were also similar but not proportional to the dose administered (17.88+/-0.91 mg/L of ampicillin and 12.92+/-0.79 mg/L of sulbactam). Both drugs had similar pharmacokinetic behaviour after i.m. administration. Since the plasma concentrations of sulbactam were consistently higher during the elimination phase of their disposition, consideration could be given to formulating the ampicillin-sulbactam combination in a ratio higher than 2:1.     

Comparative plasma ampicillin levels and bioavailability of five parenteral ampicillin formulations in ruminant calves

Summary

Plasma ampicillin concentrations were determined in an eight‐ways crossover trial involving six ruminant calves, which were treated intravenously (i.v.) with sodium ampicillin at 15.5 mg/kg and intramuscularly (i.m.) with five different ampicillin trihydrate or ampicillin anhydrate formulations at 7.7 mg/kg. The mean plasma concentration‐time curve (C_p)after intravenous ampicillin sodium administration was described biexponentially, as: C_p = 38.8 e ‐0.0268t + 0.45 e ‐0.0058t.

Intramuscular injection, into the lateral neck, of Ampikel‐20^® and Polyflex^® resulted in 100 per cent bioavailabilities within 12 h post injection (p.i.), but the biological half‐lives (t½>) were different, being 2.1 and 3.8 h, respectively. Ampikel‐20^® produced the hïghest peak plasma drug concentrations (mean C _max:4.8 μg ampicillin/ml). After intramuscular injection of Penbritin® the mean bioavailability for the first 12 h p.i. was 63 per cent, the mean t½>, was 5.9 h, and the mean C_max was 1.8 μg/ml. Treatment with Albipen^® and Duphacillin^® resulted in low plasma ampicillin levels, which were maintained for 3 to 6 days p.i., limited bioavailability during the first 12 h p.i., and a mean t½> of 22.2 and 11.9 h, respectively. Plasma concentrations of ampicillin from four hours onwards after i.m. and s.c. administration of Ampikel‐20^® at a dose level of 15.5 mg/ kg were similar.

The duration of potentially therapeutic plasma ampicillin concentrations after administration of each formulation is presented. Pre‐slaughter withdrawal times for diseased calves are suggested for the different formulations studied.     

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

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

Pharmacokinetics of sodium baicalin following intravenous and intramuscular administration to piglets

The purpose of this study was to determine the pharmacokinetics of baicalin after intravenous and intramuscular administration of sodium baicalin at 50 mg/kg to piglets. Plasma baicalin levels were determined by high‐performance liquid chromatography. The plasma concentration–time data of baicalin for both administration routes were best described by two‐compartmental open model. The area under the plasma concentration–time curve and the elimination half‐lives were 77.47 ± 6.14 µg/ml × h and 1.73 ± 0.16 hr for intravenous and 64.85 ± 5.67 µg/ml × h and 2.42 ± 0.15 hr for intramuscular administration, respectively. The apparent volume of distribution and body clearance were 1.63 ± 0.23 L/kg and 2.74 ± 0.30 L h^?1 kg^?1 for intravenous and 0.51 ± 0.10 L/kg and 0.78 ± 0.08 L h^?1 kg^?1 for intramuscular routes, respectively. An intramuscular injection of sodium baicalin in piglets resulted in rapid and complete absorption, with a mean maximal plasma concentration of 77.28 ± 7.40 µg/ml at 0.17 hr and a high absolute bioavailability of 83.73 ± 5.53%.     

Pharmacokinetics and bioavailability of cefquinome in healthy piglets

A study on bioavailability and pharmacokinetics of cefquinome in piglets was conducted after intravenous (i.v.) and intramuscular (i.m.) administrations of 2.0 mg/kg of body weight, respectively. Plasma concentrations were measured by high‐performance liquid chromatography assay with UV detector at 268‐nm wavelength. Plasma concentration–time data after i.v. administration were best fit by a two‐compartment model. The pharmacokinetic values were distribution half‐life 0.27 ± 0.21 h, elimination half‐life 1.85 ± 1.11 h, total body clearance 0.26 ± 0.08 L/kg·h, area under curve 8.07 ± 1.91 μg·h/mL and volume of distribution at steady state 0.46 ± 0.10 L/kg. Plasma concentration–time data after i.m. administration were also best fit by a two‐compartment model. The pharmacokinetic parameters were distribution half‐life 0.88 ± 0.42 h, elimination half‐life 4.36 ± 2.35 h, peak concentration 4.01 ± 0.57 μg/mL and bioavailability 95.13 ± 9.93%.     

Serum ampicillin levels in the calf: influence of dosage, route of administration and dosage form.

Holstein bull calves received ampicillin sodium by the intravenous, intramuscular and subcutaneous routes and ampicillin trihydrate by the intramuscular route, at a dosage of 5 mg/kg. In addition ampicillin sodium and ampicillin trihydrate were given at a 12 mg/kg dosage intramuscularly. The serum ampicillin concentrations were determined at five, 30, 60, 120, 180, 240 and 300 min after drug administration and at 360 min after ampicillin trihydrate injection. Intravenous administration gave a high initial level (16.2 mug/ml) at five min that declined to below 1 mug/ml by 120 min. Subcutaneous administration produced the lowest initial levels of drug but concentrations of drug detected did not differ significantly from the intramuscular administration at any sampling interval. The 12 mg/kg intramuscular ampicillin sodium dosage produced significantly higher levels than the 5 mg/kg dosage only at five min. Ampicillin trihydrate gave higher levels than ampicillin sodium at all times except 30 min (5 mg/kg) and five min (12 mg/kg). The serum ampicillin disappearance study (5 mg/kg intravenous) gave a two component bi-exponential curve. Kinetic analysis of the first component showed a C01 (theoretical initial conc) of 44.8 mug/ml, a ke1 (rate constant of disappearance) of 0.064 mug min and a t1/21 (calculated half-life) of 10.8 min. The Co2, ke2 and t1/22 of the second component were 6.2 mug/ml, 0.0157 mug/min and 46.2 min 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.     

Pharmacokinetics of dexamethasone following intra‐articular,intravenous, intramuscular,and oral administration in horses and its effects on endogenous hydrocortisone

Soma, L. R., Uboh, C. E., Liu, Y., Li, X., Robinson, M .A., Boston, R. C., Colahan, P. T. Pharmacokinetics of dexamethasone following intra‐articular, intravenous, intramuscular, and oral administration in horses and its effects on endogenous hydrocortisone. J. vet. Pharmacol. Therap.  36 , 181–191. This study investigated and compared the pharmacokinetics of intra‐articular (IA) administration of dexamethasone sodium phosphate (DSP) into three equine joints, femoropatellar (IAS), radiocarpal (IAC), and metacarpophalangeal (IAF), and the intramuscular (IM), oral (PO) and intravenous (IV) administrations. No significant differences in the pharmacokinetic estimates between the three joints were observed with the exception of maximum concentration (C_max) and time to maximum concentration (T_max). Median (range) C_max for the IAC, IAF, and IAS were 16.9 (14.6–35.4), 23.4 (13.5–73.0), and 46.9 (24.0–72.1) ng/mL, respectively. The T_max for IAC, IAF, and IAS were 1.0 (0.75–4.0), 0.62 (0.5–1.0), and 0.25 (0.08–0.25) h, respectively. Median (range) elimination half‐lives for IA and IM administrations were 3.6 (3.0–4.6) h and 3.4 (2.9–3.7) h, respectively. A 3‐compartment model was fitted to the plasma dexamethasone concentration–time curve following the IV administration of DSP; alpha, beta, and gamma half‐lives were 0.03 (0.01–0.05), 1.8 (0.34–2.3), and 5.1 (3.3–5.6) h, respectively. Following the PO administration, the median absorption and elimination half‐lives were 0.34 (0.29–1.6) and 3.4 (3.1–4.7) h, respectively. Endogenous hydrocortisone plasma concentrations declined from a baseline of 103.8 ± 29.1–3.1 ± 1.3 ng/mL at 20.0 ± 2.7 h following the administration of DSP and recovered to baseline values between 96 and 120 h for IV, IA, and IM administrations and at 72 h for the PO.     

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 ciprofloxacin in sheep after single intravenous or intramuscular administration

Summary

The disposition and urinary excretion of ciprofloxacin (CIP) following intravenous (IV) or intramuscular (IM) administration of 7.5 mg/kg body weight in sheep (n = 5) was studied. The intravenous plasma concentration curve was best described pharmacokinetically by a two‐compartment open model, while the intramuscular administration data fitted better to a one‐compartment open model. Mean elimination half‐lives after IV and IM administration were 72 and 184 minutes, respectively. The absorption of intramuscularly administered CIP in sheep was fast: maximal plasma concentration (Cmax) was reached quickly (tmax 31.93 min) and attained values of 0.69 ± 0.27 mg/l. The bioavailability was 49%. The urinary data showed a significant decrease in the elimination rate constant of CIP when CIP was administered intramuscularly. The other parameters calculated did not display differences between the two routes of administration. The results obtained suggest that when CIP was administered by the IM route in the assayed dose, it was able to maintain serum concentrations above the MIC of most common pathogens over an 8‐hour period.     

Intravenous infusion of electrolyte solution changes pharmacokinetics of drugs: pharmacokinetics of ampicillin

The pharmacokinetics of ampicillin in dogs was determined after intravenous (i.v.) bolus and constant rate infusion. Ampicillin was administered to six beagle dogs as an i.v. bolus at 20 mg/kg and as a constant rate i.v. infusion (CRI) at 20 mg/kg during 8 h (0.042 mL/min/kg) in Ringer's lactate (Hartmann's) solution. The concentrations were determined by an LC/MS/MS method. After i.v. bolus, ampicillin total body clearance, apparent volume of distribution at steady‐state, mean residence time (MRT), and half‐life were 4.53 ± 0.70 mL/min/kg, 0.275 ± 0.044 L/kg, 61 ± 13 min, and 111 (85–169) min, respectively. The corresponding parameters calculated after CRI were 13.5 ± 1.06 mL/min/kg, 0.993 ± 0.415 L/kg, 73 ± 27 min, and 49 (31–69) min. Ampicillin concentration decreased by 30% in the Ringer's lactate infusion solution mostly during the first hour after preparation of the solution. Constant rate infusion of Ringer's lactate solution during 8 h caused significant changes in ampicillin pharmacokinetics. The results suggested that special attention should be given to drug pharmacokinetics when co‐administered intravenously with electrolyte solutions.     

Pharmacokinetics and pharmacodynamics comparison between subcutaneous and intravenous butorphanol administration in horses

The study objective was to compare butorphanol pharmacokinetics and physiologic effects following intravenous and subcutaneous administration in horses. Ten adult horses received 0.1 mg/kg butorphanol by either intravenous or subcutaneous injections, in a randomized crossover design. Plasma concentrations of butorphanol were measured at predetermined time points using highly sensitive liquid chromatography–tandem mass spectrometry assay (LC‐MS/MS). Demeanor and physiologic variables were recorded. Data were analyzed with multivariate mixed‐effect model on ranks (P ≤ 0.05). For subcutaneous injection, absorption half‐life and peak plasma concentration of butorphanol were 0.10 ± 0.07 h and 88 ± 37.4 ng/mL (mean ± SD), respectively. Bioavailability was 87%. After intravenous injection, mean ± SD butorphanol steady‐state volume of distribution and clearance was 1.2 ± 0.96 L/kg and 0.65 ± 0.20 L/kg/h, respectively. Terminal half‐lives for butorphanol were 2.31 ± 1.74 h and 5.29 ± 1.72 h after intravenous and subcutaneous administrations. Subcutaneous butorphanol reached and maintained target plasma concentrations >10 ng/mL for 2 ± 0.87 h (Mean ± SD), with less marked physiologic and behavioral effects compared to intravenous injection. Subcutaneous butorphanol administration is an acceptable alternative to the intravenous route in adult horses.     

Pharmacokinetics of cefuroxime after intravenous,intramuscular, and subcutaneous administration to dogs

Cefuroxime pharmacokinetic profile was investigated in 6 Beagle dogs after single intravenous, intramuscular, and subcutaneous administration at a dosage of 20 mg/kg. Blood samples were withdrawn at predetermined times over a 12‐h period. Cefuroxime plasma concentrations were determined by HPLC. Data were analyzed by compartmental analysis. Peak plasma concentration (C_max), time‐to‐peak plasma concentration (T_max), and bioavailability for the intramuscular and subcutaneous administration were (mean ± SD) 22.99 ± 7.87 μg/mL, 0.43 ± 0.20 h, and 79.70 ± 14.43% and 15.37 ± 3.07 μg/mL, 0.99 ± 0.10 h, and 77.22 ± 21.41%, respectively. Elimination half‐lives and mean residence time for the intravenous, intramuscular, and subcutaneous administration were 1.12 ± 0.19 h and 1.49 ± 0.21 h; 1.13 ± 0.13 and 1.79 ± 0.24 h; and 1.04 ± 0.23 h and 2.21 ± 0.23 h, respectively. Significant differences were found between routes for K_a, MAT, C_max, T_max, t_½(a), and MRT. T > MIC = 50%, considering a MIC of 1 μg/mL, was 11 h for intravenous and intramuscular administration and 12 h for the subcutaneous route. When a MIC of 4 μg/mL is considered, T > MIC = 50% for intramuscular and subcutaneous administration was estimated in 8 h.     

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

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

Pharmacokinetics and bioavailability of sulfadiazine and trimethoprim following intravenous, intramuscular and oral administration in ostriches (Struthio camelus)

A pharmacokinetic and bioavailability study of sulfadiazine combined with trimethoprim (sulfadiazine/trimethoprim) was carried out in fifteen healthy young ostriches after intravenous (i.v.), intramuscular (i.m.) and oral administration at a total dose of 30 mg/kg body weight (bw) (25 and 5 mg/kg bw of sulfadiazine and trimethoprim, respectively). The study followed a single dose, three periods, cross‐over randomized design. The sulfadiazine/trimethoprim combination was administered to ostriches after an overnight fasting on three treatment days, each separated by a 2‐week washout period. Blood samples were collected at 0 (pretreatment), 0.08, 0.25, 0.50, 1, 2, 4, 6, 8, 12, 24 and 48 h after drug administration. Following i.v. administration, the elimination half‐life (t_1/2β), the mean residence time (MRT), volume of distribution at steady‐state (V_d(ss)), volume of distribution based on terminal phase (V_d(z)), and the total body clearance (Cl_B) were (13.23 ± 2.24 and 1.95 ± 0.19 h), (10.06 ± 0.33 and 2.17 ± 0.20 h), (0.60 ± 0.08, and 2.35 ± 0.14 L/kg), (0.79 ± 0.12 and 2.49 ± 0.14 L/kg) and (0.69 ± 0.03 and 16.12 ± 1.38 mL/min/kg), for sulfadiazine and trimethoprim, respectively. No significant difference in C_max (35.47 ± 2.52 and 37.50 ± 3.39 μg/mL), t_max (2.47 ± 0.31 and 2.47 ± 0.36 h), t_½β (11.79 ± 0.79 and 10.96 ± 0.56 h), V_d(z)/F (0.77 ± 0.06 and 0.89 ± 0.07 L/kg), Cl_B/F (0.76 ± 0.04 and 0.89 ± 0.07) and MRT (12.39 ± 0.40 and 12.08 ± 0.36 h) were found in sulfadiazine after i.m. and oral dosing, respectively. There were also no differences in C_max (0.71 ± 0.06 and 0.78 ± 0.10 μg/mL), t_max (2.07 ± 0.28 and 3.27 ± 0.28 h), t_½β (3.30 ± 0.25 and 3.83 ± 0.33 h), V_d(z)/F (6.2 ± 0.56 and 6.27 ± 0.77 L/kg), Cl_B/F (21.9 ± 1.46 and 18.83 ± 1.72) and MRT (3.68 ± 0.19 and 4.34 ± 0.14 h) for trimethoprim after i.m. and oral dosing, respectively. The absolute bioavailability (F) was 95.41% and 86.20% for sulfadiazine and 70.02% and 79.58% for trimethoprim after i.m. and oral 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.     

Florfenicol pharmacokinetics in healthy adult alpacas after subcutaneous and intramuscular injection

Holmes, K., Bedenice, D., Papich, M. G. Florfenicol pharmacokinetics in healthy adult alpacas after subcutaneous and intramuscular injection. J. vet. Pharmacol. Therap.  35 , 382–388. A single dose of florfenicol (Nuflor^®) was administered to eight healthy adult alpacas at 20 mg/kg intramuscular (i.m.) and 40 mg/kg subcutaneous (s.c.) using a randomized, cross‐over design, and 28‐day washout period. Subsequently, 40 mg/kg florfenicol was injected s.c. every other day for 10 doses to evaluate long‐term effects. Maximum plasma florfenicol concentrations (C_max, measured via high‐performance liquid chromatography) were achieved rapidly, leading to a higher C_max of 4.31 ± 3.03 μg/mL following administration of 20 mg/kg i.m. than 40 mg/kg s.c. (C_max: 1.95 ± 0.94 μg/mL). Multiple s.c. dosing at 48 h intervals achieved a C_max of 4.48 ± 1.28 μg/mL at steady state. The area under the curve and terminal elimination half‐lives were 51.83 ± 11.72 μg/mL·h and 17.59 ± 11.69 h after single 20 mg/kg i.m. dose, as well as 99.78 ± 23.58 μg/mL·h and 99.67 ± 59.89 h following 40 mg/kg injection of florfenicol s.c., respectively. Florfenicol decreased the following hematological parameters after repeated administration between weeks 0 and 3: total protein (6.38 vs. 5.61 g/dL, P < 0.0001), globulin (2.76 vs. 2.16 g/dL, P < 0.0003), albumin (3.61 vs. 3.48 g/dL, P = 0.0038), white blood cell count (11.89 vs. 9.66 × 10³/μL, P < 0.044), and hematocrit (27.25 vs. 24.88%, P < 0.0349). Significant clinical illness was observed in one alpaca. The lowest effective dose of florfenicol should thus be used in alpacas and limited to treatment of highly susceptible pathogens.