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 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.     

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 difloxacin after intravenous, intramuscular, and intragastric administration to horses

OBJECTIVE: To study the pharmacokinetics of difloxacin (5 mg/kg) following IV, IM, and intragastric (IG) administration to healthy horses. ANIMALS: 6 healthy mature horses. PROCEDURES: A crossover study design with 3 phases was used (15-day washout periods between treatments). An injectable formulation of difloxacin (5%) was administered IV and IM in single doses (5 mg/kg); for IG administration, an oral solution was prepared and administered via nasogastric tube. Blood samples were collected before and at intervals after each administration. A high-performance liquid chromatography assay with fluorescence detection was used to determine plasma difloxacin concentrations. Pharmacokinetic parameters of difloxacin were analyzed. Plasma creatine kinase activity was monitored to assess tissue damage. RESULTS: Difloxacin plasma concentration versus time data after IV administration were best described by a 2-compartment open model. The disposition of difloxacin following IM or IG administration was best described by a 1-compartment model. Mean half-life for difloxacin administered IV, IM, and IG was 2.66, 5.72, and 10.75 hours, respectively. Clearance after IV administration was 0.28 L/kg.h. After IM administration, the absolute mean +/- SD bioavailability was 95.81 +/- 3.11% and maximum plasma concentration (Cmax) was 1.48 +/- 0.12 mg/L. After IG administration, the absolute bioavailability was 68.62 +/- 10.60% and Cmax was 0.732 +/- 0.05 mg/L. At 12 hours after IM administration, plasma creatine kinase activity had increased 7-fold, compared with the preinjection value. CONCLUSIONS AND CLINICAL RELEVANCE: Data suggest that difloxacin is likely to be effective for treating susceptible bacterial infections in horses.     

Pharmacokinetics of butorphanol tartrate in red-tailed hawks (Buteo jamaicensis) and great horned owls (Bubo virginianus)

OBJECTIVE: To determine the pharmacokinetics of butorphanol tartrate after IV and IM single-dose administration in red-tailed hawks (RTHs) and great horned owls (GHOs). ANIMALS: 6 adult RTHs and 6 adult GHOs. PROCEDURES: Each bird received an injection of butorphanol (0.5 mg/kg) into either the right jugular vein (IVj) or the pectoral muscles in a crossover study (1-week interval between treatments). The GHOs also later received butorphanol (0.5 mg/kg) via injection into a medial metatarsal vein (IVm). During each 24-hour postinjection period, blood samples were collected from each bird; plasma butorphanol concentrations were determined via liquid chromatography-mass spectrometry. RESULTS: 2- and 1-compartment models best fit the IV and IM pharmacokinetic data, respectively, in both species. Terminal half-lives of butorphanol were 0.94 +/- 0.30 hours (IVj) and 0.94 +/- 0.26 hours (IM) for RTHs and 1.79 +/- 1.36 hours (IVj), 1.84 +/- 1.56 hours (IM), and 1.19 +/- 0.34 hours (IVm) for GHOs. In GHOs, area under the curve (0 to infinity) for butorphanol after IVj or IM administration exceeded values in RTHs; GHO values after IM and IVm administration were less than those after IVj administration. Plasma butorphanol clearance was significantly more rapid in the RTHs. Bioavailability of butorphanol administered IM was 97.6 +/- 33.2% (RTHs) and 88.8 +/- 4.8% (GHOs). CONCLUSIONS AND CLINICAL RELEVANCE: In RTHs and GHOs, butorphanol was rapidly absorbed and distributed via all routes of administration; the drug's rapid terminal half-life indicated that published dosing intervals for birds may be inadequate in RTHs and GHOs.     

Disposition and excretion of flunixin meglumine in horses

The disposition of flunixin meglumine administered IV at a dosage of 1.1 mg/kg was described by a 2-compartment model; the alpha and beta half-lives (t1/2) were 0.61 and 1.5 hours, respectively. When administered IV at a rate of 2.2 mg/kg, the disposition was best described by a 3-compartment model, and the alpha, beta, and lambda t1/2 were 0.16, 1.52, and 6.00 hours, respectively. The zero-time plasma concentrations after flunixin meglumine was administered at 1.1 and 2.2 mg/kg were 9.3 +/- 0.76 and 21.5 +/- 7.4 mg/L, respectively. The bioavailability after oral administration of 1.1 mg/kg was 85.8%. The absorption t1/2 was 0.57 hours, with a peak concentration of 2.50 +/- 1.25 mg/L. The cumulative urinary recoveries for IV and oral administrations were 61.0% and 63.3%, respectively, of the dose for the 12-hour collection period. The final asymptotic points of urine excretion after IV and oral administrations were 406.4 +/- 65.5 and 357.7 +/- 53.5 mg, respectively, which represented 75.5 and 77.5% of the drug accounted for between 30 and 35 hours after administration. Flunixin meglumine was rapidly excreted in urine over a 2- to 4-hour period after drug administration and was highly bound to protein in plasma.     

Pharmacokinetics of flunixin meglumine in lactating cattle after single and multiple intramuscular and intravenous administrations

The pharmacokinetics of flunixin were studied in 6 adult lactating cattle after administration of single IV and IM doses at 1.1 mg/kg of body weight. A crossover design was used, with route of first administration in each cow determined randomly. Plasma and milk concentrations of total flunixin were determined by use of high-pressure liquid chromatography, using an assay with a lower limit of detection of 50 ng of flunixin/ml. The pharmacokinetics of flunixin were best described by a 2-compartment, open model. After IV administration, mean plasma flunixin concentrations rapidly decreased from initial concentrations of greater than 10 micrograms/ml to nondetectable concentrations at 12 hours after administration. The distribution phase was short (t1/2 alpha, harmonic mean = 0.16 hours) and the elimination phase was more prolonged (t1/2 beta, harmonic mean = 3.14 hours). Mean +/- SD clearance after IV administration was 2.51 +/- 0.96 ml/kg/min. After IM administration, the harmonic mean for the elimination phase (t1/2 beta) was prolonged at 5.20 hours. Bioavailability after IM dosing gave a mean +/- SD (n = 5) of 76.0 +/- 28.0%. Adult, lactating cows (n = 6) were challenge inoculated with endotoxin as a model of acute coliform mastitis. After multiple administration (total of 7 doses; first IV, remainder IM) of 1.1 mg/kg doses of flunixin at 8-hour intervals, plasma flunixin concentrations were approximately 1 microgram/ml at 2 hours after each dosing and 0.5 micrograms/ml just prior to each dosing. Flunixin was not detected in milk at any sampling during the study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of clindamycin phosphate in dogs after single intravenous and intramuscular administrations.

Clindamycin phosphate was administered to dogs at dosage of 11 mg/kg of body weight via IV and IM routes. The disposition curve for IV administration was best represented as a 2-compartment open model. Mean elimination half life was 194.6 +/- 24.5 minutes for IV administration and 234.8 +/- 27.3 minutes for IM administration. Bioavailability after IM administration was 87%. Dosage of 11 mg/kg, IV, given every 8 hours, provided serum concentration of clindamycin that exceeded the minimal inhibitory concentration for all Staphylococcus spp, as well as most pathogenic anaerobes, throughout the dosing interval. Intramuscular administration induced signs of pain and cannot be recommended.     

Pharmacokinetics of enrofloxacin after intravenous and intramuscular injection in rabbits.

The pharmacokinetics and bioavailability of enrofloxacin were determined after IV and IM administration of 5 mg/kg of body weight to 6 healthy adult rabbits. Using nonlinear least-squares regression methods, data obtained were best described by a 2-compartment open model. After IV administration, a rapid distribution phase was followed by a slower elimination phase, with a half-life of 131.5 +/- 17.6 minutes. The mean body clearance rate was 22.8 +/- 6.8 ml/min/kg, and the mean volume of distribution was 3.4 +/- 0.9 L/kg. This large volume of distribution and the K12/K21 ratio close to 1, indicated that enrofloxacin was widely distributed in the body, but not retained in tissues. After a brief lag period (6.2 +/- 2.86 min), IM absorption was rapid (4.1 +/- 1.3 min) and almost complete. The mean extent of IM absorption was 92 +/- 11%, and maximal plasma concentration of 3.04 +/- 0.34 micrograms/ml was detected approximately 10 minutes after administration.     

Pharmacokinetics of single-dose intravenous or intramuscular administration of gentamicin in roosters

Healthy mature roosters (n = 10) were given gentamicin (5 mg/kg of body weight, IV) and, 30 days later, another dose IM. Serum concentrations of gentamicin were determined over 60 hours after each drug dosing, using a radioimmunoassay. Using nonlinear least-square regression methods, the combined data of IV and IM treatments were best fitted by a 2-compartment open model. The mean distribution phase half-life was 0.203 +/- 0.075 hours (mean +/- SD) and the terminal half-life was 3.38 +/- 0.62 hours. The volume of the central compartment was 0.0993 +/- 0.0097 L/kg, volume of distribution at steady state was 0.209 +/- 0.013 L/kg, and the total body clearance was 46.5 +/- 7.9 ml/h/kg. Intramuscular absorption was rapid, with a half-life for absorption of 0.281 +/- 0.081 hours. The extent of IM absorption was 95 +/- 18%. Maximal serum concentration of 20.68 +/- 2.10 micrograms/ml was detected at 0.62 +/- 0.18 hours after the dose. Kinetic calculations predicted that IM injection of gentamicin at a dosage of 4 mg/kg, q 12 h, and 1.5 mg/kg, q 8 h, would provide average steady-state serum concentrations of 6.82 and 3.83 micrograms/ml, with minimal steady-state serum concentrations of 1.54 and 1.50 micrograms/ml and maximal steady-state serum concentrations of 18.34 and 7.70 micrograms/ml, respectively.     

Pharmacokinetics of ceftiofur sodium after intramuscular or subcutaneous administration in green iguanas (Iguana iguana)

OBJECTIVE: To determine the pharmacokinetics of ceftiofur sodium after IM and SC administration in green iguanas. ANIMALS: 6 male and 4 female adult green iguanas. PROCEDURE: In a crossover design, 5 iguanas received a single dose of ceftiofur sodium (5 mg/kg) IM, and 5 iguanas received the same dose SC. Blood samples were taken at 0, 20, and 40 minutes and 1, 2, 4, 8, 24, 48, and 72 hours after administration. After a 10-week washout period, each iguana was given the same dose via the reciprocal administration route, and blood was collected in the same fashion. Ceftiofur free-acid equivalents were measured via high-performance liquid chromatography. RESULTS: The first phase intercepts were significantly different between the 2 administration routes. Mean maximum plasma concentration was significantly higher with the IM (28.6 +/- 8.0 microg/mL) than the SC (18.6 +/- 8.3 microg/mL) administration route. There were no significant differences between terminal half-lives (harmonic mean via IM route, 15.7 +/- 4.7 hours; harmonic mean via SC route, 19.7 +/- 6.7 hours) and mean areas under the curve measured to the last time point (IM route, 11,722 +/- 7,907 microg x h/mL; SC route, 12,143 +/- 9,633 microg x h/mL). Ceftiofur free-acid equivalent concentrations were maintained > or = 2 microg/mL for > 24 hours via both routes. CONCLUSIONS AND CLINICAL RELEVANCE: A suggested dosing schedule for ceftiofur sodium in green iguanas for microbes susceptible at > 2 microg/mL would be 5 mg/kg, IM or SC, every 24 hours.     

Pharmacokinetic properties of enrofloxacin in rabbits.

The pharmacokinetic properties of the fluoroquinolone antimicrobial enrofloxacin were studied in New Zealand White rabbits. Four rabbits were each given enrofloxacin as a single 5 mg/kg of body weight dosage by IV, SC, and oral routes over 4 weeks. Serum antimicrobial concentrations were determined for 24 hours after dosing. Compartmental modeling of the IV administration indicated that a 2-compartment open model best described the disposition of enrofloxacin in rabbits. Serum enrofloxacin concentrations after SC and oral dosing were best described by a 1- and 2-compartment model, respectively. Overall elimination half-lives for IV, SC, and oral routes of administration were 2.5, 1.71, and 2.41 hours, respectively. The half-life of absorption for oral dosing was 26 times the half-life of absorption after SC dosing (7.73 hours vs 0.3 hour). The observed time to maximal serum concentration was 0.9 hour after SC dosing and 2.3 hours after oral administration. The observed serum concentrations at these times were 2.07 and 0.452 micrograms/ml, respectively. Mean residence times were 1.55 hours for IV injections, 1.46 hours for SC dosing, and 8.46 hours for oral administration. Enrofloxacin was widely distributed in the rabbit as suggested by the volume of distribution value of 2.12 L/kg calculated from the IV study. The volume of distribution at steady-state was estimated at 0.93 L/kg. Compared with IV administration, bioavailability was 77% after SC dosing and 61% for gastrointestinal absorption. Estimates of predicted average steady-state serum concentrations were 0.359, 0.254, and 0.226 micrograms/ml for IV, SC, and oral administration, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

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

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

Pharmacokinetics and bioavailability of ceftriaxone administered intravenously and intramuscularly to calves

Ceftriaxone was administered to Israeli-Friesian male calves by IV and IM routes. The antibiotic was administered IV (10 mg/kg) to 10 calves and IM to 23 calves; 8 were given the antibiotic at the rate of 10 mg/kg of body weight, 5 were given 20 mg/kg, and 10 were given 10 mg/kg, together with probenecid at 40 mg/kg. Serum concentration vs time profiles measured after IV and IM administration were analyzed by use of statistical moment theory. The following mean values +/- SD were found: elimination half-life (t1/2) was 83.8 +/- 8.6 minutes after IV administration and significantly longer 116.8 +/- 20.5 minutes (P less than 0.001) after IM administration at 10 mg/kg. The t1/2 was increased to 141.3 +/- 24.4 minutes by the coadministration of probenecid and to 145.0 +/- 48.2 minutes by doubling the IM dosage to 20 mg/kg. The total body clearance was 3.39 +/- 0.42 ml/min/kg and the renal clearance 2.37 +/- 0.74 ml/min/kg. The specific volume of distribution was 0.2990 +/- 0.0510 L/kg. The average mean residence time (MRT) was 94.0 +/- 12.3 minutes after IV administration and 137.6 +/- 19.9 minutes after IM administration of ceftriaxone at 10 mg/kg. The MRT was increased to 198 +/- 48.8 minutes by the coadministration of probenecid and to 191.0 +/- 59.4 minutes by doubling the IM dose. The former value was significantly different from the MRT after IM administration of the antibiotic at 10 mg/kg. Bioavailability of ceftriaxone after IM administration at 10 mg/kg and at 20 mg/kg was 78% and 83%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of norfloxacin in dogs after single intravenous and single and multiple oral administrations of the drug

Norfloxacin was given to 6 healthy dogs at a dosage of 5 mg/kg of body weight IV and orally in a complete crossover study, and orally at dosages of 5, 10, and 20 mg/kg to 6 healthy dogs in a 3-way crossover study. For 24 hours, serum concentration was monitored serially after each administration. Another 6 dogs were given 5 mg of norfloxacin/kg orally every 12 hours for 14 days, and serum concentration was determined serially for 12 hours after the first and last administration of the drug. Complete blood count and serum biochemical analysis were performed before and after 14 days of oral norfloxacin administration, and clinical signs of drug toxicosis were monitored twice daily during norfloxacin administration. Urine concentration of norfloxacin was determined periodically during serum acquisition periods. Norfloxacin concentration was determined, using high-performance liquid chromatography with a limit of detection of 25 ng of norfloxacin/ml of serum or urine. Serum norfloxacin pharmacokinetic values after single IV dosing in dogs were best modeled, using a 2-compartment open model, with distribution and elimination half-lives of 0.467 and 3.56 hours (harmonic means), respectively. Area-derived volume of distribution (Vd area) was 1.77 +/- 0.69 L/kg (arithmetic mean +/- SD), and serum clearance (Cls) was 0.332 +/- 0.115 L/h/kg. Mean residence time was 4.32 +/- 0.98 hour. Comparison of the area under the curve (AUC; derived, using model-independent calculations) after iv administration (5 mg/kg) with AUC after oral administration (5 mg/kg) in the same dogs indicated bioavailability of 35.0 +/- 46.1%, with a mean residence time after oral administration of 5.71 +/-2.24 hours. Urine concentration was 33.8 +/- 15.3 micrograms/ml at 4 hours after a single dose of 5 mg/kg given orally, whereas concentration after 20 mg/kg was given orally was 56.8 +/- 18.0 micrograms/ml at 6 hours after dosing. Twelve hours after drug administration, urine concentration was 47.4 +/- 20.6 micrograms/ml after the 5-mg/kg dose and 80.6 +/- 37.7 micrograms/ml after the 20/mg/kg dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of imipenem in dogs

OBJECTIVE: To determine the plasma pharmacokinetics of imipenem (5 mg/kg) after single-dose IV, IM, and SC administrations in dogs and assess the ability of plasma samples to inhibit the growth of Escherichia coli in vitro. ANIMALS: 6 adult dogs. PROCEDURE: A 3-way crossover design was used. Plasma concentrations of imipenem were measured after IV, IM, and SC administration by use of high-performance liquid chromatography. An agar well antimicrobial assay was performed with 3 E coli isolates that included a reference strain and 2 multidrug-resistant clinical isolates. RESULTS: Plasma concentrations of imipenem remained above the reported minimum inhibitory concentration for E coli (0.06 to 0.25 microg/mL) for a minimum of 4 hours after IV, IM, and SC injections. Harmonic mean and pseudo-standard deviation half-life of imipenem was 0.80 +/- 0.23, 0.92 +/- 0.33, and 1.54 +/- 1.02 hours after IV, IM, and SC administration, respectively. Maximum plasma concentrations (Cmax) of imipenem after IM and SC administration were 13.2 +/- 4.06 and 8.8 +/- 1.7 mg/L, respectively. Time elapsed from drug administration until Cmax was 0.50 +/- 0.16 hours after IM and 0.83 +/- 0.13 hours after SC injection. Growth of all 3 E coli isolates was inhibited in the agar well antimicrobial assay for 2 hours after imipenem administration by all routes. CONCLUSIONS AND CLINICAL RELEVANCE: Imipenem is rapidly and completely absorbed from intramuscular and subcutaneous tissues and effectively inhibits in vitro growth of certain multidrug-resistant clinical isolates of E coli.     

Pharmacokinetics of single-dose administration of moxalactam in unweaned calves

Twenty-nine healthy 17- to 29-day-old unweaned Israeli-Friesian male calves were each given a single IV or IM injection of 10 or 20 mg of moxalactam disodium/kg of body weight. Serum concentrations were measured serially during a 12-hour period. Serum concentration vs time profiles were analyzed by use of linear least-squares regression analysis and the statistical moment theory. The elimination half-lives after IV administration were 143.7 +/- 30.2 minutes and 155.5 +/- 10.5 minutes (harmonic mean +/- SD) at dosages of 10 and 20 mg of moxalactam/kg of body weight, respectively. Corresponding mean residence time values were 153.1 +/- 26.8 minutes and 169.9 +/- 19.3 minutes (arithmetic mean +/- SD). Mean residence time values after IM administration were 200.4 +/- 17.5 minutes and 198.4 +/- 19.9 minutes at dosages of 10 and 20 mg/kg, respectively. The volumes of distribution at steady state were 0.285 +/- 0.073 L/kg and 0.313 +/- 0.020 L/kg and total body clearance values were 1.96 +/- 0.69 ml/min/kg and 1.86 +/- 0.18 ml/min/kg after administration of dosages of 10 and 20 mg/kg, respectively. Moxalactam was rapidly absorbed from the IM injection site and peak serum concentrations occurred at 1 hour. The estimated bioavailability ranged from 69.8 to 79.1%. The amount of serum protein binding was 53.4, 55.0, and 61.5% when a concentration of moxalactam was at 50, 10, and 2 micrograms/ml, respectively. The minimal inhibitory concentrations of moxalactam ranged from 0.01 to 0.2 micrograms/ml against Salmonella and Escherichia coli strains and from 0.005 to 6.25 micrograms/ml against Pasteurella multocida strains.     

Pharmacokinetics of enrofloxacin administered intravenously and orally to foals

OBJECTIVE: To determine the pharmacokinetics of enrofloxacin administered IV and orally to foals. ANIMALS: 5 clinically normal foals. PROCEDURE: A 2-dose cross-over trial with IV and oral administration was performed. Enrofloxacin was administered once IV (5 mg/kg of body weight) to 1-week-old foals, followed by 1 oral administration (10 mg/kg) after a 7-day washout period. Blood samples were collected for 48 hours after the single dose IV and oral administrations and analyzed for plasma enrofloxacin and ciprofloxacin concentrations by use of high-performance liquid chromatography. RESULTS: For IV administration, mean +/- SD total area under the curve (AUC0-infinity) was 48.54 +/- 10.46 microg x h/ml, clearance was 103.72 +/- 0.06 ml/kg/h, half-life (t1/2beta) was 17.10 +/- 0.09 hours, and apparent volume of distribution was 2.49 +/- 0.43 L/kg. For oral administration, AUC0-infinity was 58.47 +/- 16.37 microg x h/ml, t1/2beta was 18.39 +/- 0.06 hours, maximum concentration (Cmax) was 2.12 +/- 00.51 microg/ml, time to Cmax was 2.20 +/- 2.17 hours, mean absorption time was 2.09 +/- 0.51 hours, and bioavailability was 42 +/- 0.42%. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with adult horses given 5 mg of enrofloxacin/kg IV, foals have higher AUC0-infinity, longer t1/2beta, and lower clearance. Concentration of ciprofloxacin was negligible. Using a target Cmax to minimum inhibitory concentration ratio of 1:8 to 1:10, computer modeling suggests that 2.5 to 10 mg of enrofloxacin/kg administered every 24 hours would be effective in foals, depending on minimum inhibitory concentration of the pathogen.     

Pharmacokinetics of single doses of digoxin administered intravenously to ducks, roosters, and turkeys

A single dose of digoxin was injected, IV, into 5 mature male turkeys (0.066 mg/kg of body weight), 8 male ducks (0.066 mg/kg), and 6 roosters (0.33 mg/kg). Twenty-three serial venous blood samples were collected before (baseline) and after the administration of digoxin to turkeys, ducks, and roosters. Plasma concentrations of digoxin were determined in duplicate by a radioimmunoassay that was validated for avian species. The plasma concentrations were best fitted by a 3 (turkeys, ducks)- and 2 (roosters)-compartment open model, with first-order elimination from the central compartment. Significant (P less than 0.05) kinetic differences were determined among species. Mean half-life (t1/2) for ducks, roosters, and turkeys were 8.30 +/- 2.70 (mean +/- SD), 6.67 +/- 3.50, and 23.7 +/- 4.8 hours, respectively. The volume of distribution at steady state (Vss) was 14.7 +/- 2.9, 3.13 +/- 0.49, and 2.27 +/- 0.36 L/kg, and total body clearance (CL) of drug was 1.54 +/- 0.43, 0.461 +/- 0.187, and 0.136 +/- 0.022 L/h/kg for ducks, roosters, and turkeys, respectively. The mean residence time was 10.3 +/- 3.9, 8.37 +/- 4.97, and 16.8 +/- 2.2 hours, respectively. Volume of distribution at steady state and CL in ducks were several fold higher than that in turkeys. The terminal half-life of digoxin determined for ducks and roosters in this study was considerably shorter than those previously reported for several mammalian species.     

Pharmacokinetics after intravenous, intramuscular and subcutaneous administration of difloxacin in sheep

The disposition kinetics of difloxacin, a fluoroquinolone antibiotic, after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration were determined in sheep at a single dose of 5mg/kg. The concentration-time data were analysed by compartmental (after IV dose) and non-compartmental pharmacokinetics method (after IV, IM and SC administration). Plasma concentrations of difloxacin were determined by high performance liquid chromatography with fluorescence detection. Steady-state volume of distribution (V(ss)) and clearance (Cl) of difloxacin after IV administration were 1.68+/-0.21L/kg and 0.21+/-0.03L/hkg, respectively. Following IM and SC administration difloxacin achieved maximum plasma concentration of 1.89+/-0.55 and 1.39+/-0.14mg/L at 2.42+/-1.28 and 5.33+/-1.03h, respectively. The absolute bioavailabilities after IM and SC routes were 99.92+/-26.50 and 82.35+/-25.65%, respectively. Based on these kinetic parameters, difloxacin is likely to be effective in sheep.