Pharmacokinetics, bioavailability, and in vitro antibacterial activity of rifampin in the horse

The pharmacokinetics and bioavailability of rifampin were determined after IV (10 mg/kg of body weight) and intragastric (20 mg/kg of body weight) administration to 6 healthy, adult horses. After IV administration, the disposition kinetics of rifampin were best described by a 2-compartment open model. A rapid distribution phase was followed by a slower elimination phase, with a half-life (t1/2[beta]) of 7.27 +/- 1.11 hours. The mean body clearance was 1.49 +/- 0.41 ml/min.kg, and the mean volume of distribution was 932 +/- 292 ml/kg, indicating that rifampin was widely distributed in the body. After intragastric administration of rifampin in aqueous suspension, a brief lag period (0.31 +/- 0.09 hour) was followed by rapid, but incomplete, absorption (t1/2[a] = 0.51 +/- 0.32 hour) and slow elimination (t1/2[d] = 11.50 +/- 1.55 hours). The mean bioavailability (fractional absorption) of the administered dose during the first 24 hours was 53.94 +/- 18.90%, and we estimated that 70.0 +/- 23.6% of the drug would eventually be absorbed. The mean peak plasma rifampin concentration was 13.25 +/- 2.70 micrograms/ml at 2.5 +/- 1.6 hours after dosing. All 6 horses had plasma rifampin concentrations greater than 2 micrograms/ml by 45 minutes after dosing; concentrations greater than 3 micrograms/ml persisted for at least 24 hours. Mean plasma rifampin concentrations at 12 and 24 hours after dosing were 6.86 +/- 1.69 micrograms/ml and 3.83 +/- 0.87 micrograms/ml, respectively. We tested 162 isolates of 16 bacterial species cultured from clinically ill horses for susceptibility to rifampin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of vitamin E concentrations in serum and cerebrospinal fluid of horses following oral administration of vitamin E

OBJECTIVE: To determine concentrations of alpha-tocopherol in serum and CSF of healthy horses following administration of supplemental vitamin E in feed. ANIMALS: 10 healthy adult horses. PROCEDURES: Horses were allocated to receive supplemental d-alpha-tocopherol (1,000 U/d [group A; n=5] or 10,000 U/d [group B; 5]) in feed for 10 days. Blood samples were collected before (baseline), during, and at intervals for 10 days after discontinuation of vitamin E administration for assessment of serum alpha-tocopherol concentration. Cerebrospinal fluid samples were collected prior to and 24 hours after cessation of vitamin E administration. Alpha-tocopherol concentrations in serum and CSF samples were analyzed via high-performance liquid chromatography; changes in those values during the treatment period were compared between groups, and the relationship of serum and CSF alpha-tocopherol concentrations was evaluated. RESULTS: In both groups, serum alpha-tocopherol concentration increased significantly from baseline during vitamin E administration; values in group B were significantly greater than those in group A during and after treatment. At the end of vitamin E administration, CSF alpha-tocopherol concentration was not significantly greater than the baseline value in either group; however, the increase in CSF concentration was significant when the group data were combined and analyzed. Serum and CSF alpha-tocopherol concentrations were significantly correlated at baseline for all horses, but were not strongly correlated after 10 days of vitamin E administration. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy horses, daily oral administration of supplemental vitamin E in feed resulted in increases in serum and CSF alpha-tocopherol concentrations.     

Kinetic behavior of three preparations of alpha-tocopherol after oral administration to postpubertal heifers

OBJECTIVE: To assess the kinetic behavior of 3 preparations of alpha-tocopherol (vitamin E) after oral administration to heifers. ANIMALS: 8 postpubertal Friesian heifers. PROCEDURE: A single oral bolus of 5,000 U of alpha-tocopherol in oil or encapsulated in liposomes or cyclodextrin was administered to each cow, using a 4 X 4 design with 8 days between treatments. Blood samples for kinetic analyses were obtained at various times for 168 hours after treatment. RESULTS: Mean (+/- SEM) maximal plasma concentrations of alpha-tocopherol were 4.86 +/- 0.49 microg/ml, 5.03 +/- 0.39 microg/ml, and 5.08 +/- 0.56 microg/ml after administration of oil, liposomal, and cyclodextrin preparations, respectively. Plasma concentrations peaked 21 to 34 hours after administration. The disappearance rate constant (Kd) was less after administration of alpha-tocopherol encapsulated in liposomes, compared with the other 2 preparations. Area under the concentration versus time curve was greater after administration of either encapsulated form of alpha-tocopherol, compared with alpha-tocopherol in oil, but these differences were not significant. CONCLUSIONS AND CLINICAL RELEVANCE: The lower Kd determined for alpha-tocopherol encapsulated in liposomes suggests that this formulation may result in longer persistance of the vitamin in plasma than the other 2 preparations. Dietary supplementation with alpha-tocopherol encapsulated in liposomes may enhance plasma availability of this vitamin in cattle and could be useful during periods of increased vitamin E requirements, such as parturition and early stages of life.     

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.     

The effect of administration of vitamin E on levels of serum immunoglobulins and levels of phagocytic activity]

The effect of peroral administration and parenteral implantation of vitamin E was followed as exerted on the concentration of total serum immunoglobulins and phagocytic activity of blood leucocytes in calves. Twelve calves at the age of maximally 14 days with the average live weight of 41.2 kg were included in an experiment with peroral administration; six of them were given Combinal E (Tocoferolum aceticum 40 mg in 1 ml) at a dose of 20 mg tocopherol acetate per kg live weight. Sixteen calves at the age of three months and with the average live weight of 112.6 kg were included in the second trial. The Erevit preparation was implanted intramuscularly to eight calves at the same dose as in the first experiment (Tocoferolum aceticum 300 mg in 1 ml solutions oleosae). The animals of control groups in both experiments were administered sunflower oil as a placebo, namely at the same amount as the above-mentioned preparations (no oil treatment for peroral administration, heat and pressure treatments of oil for intramuscular implantation). All the preparations lead to a significant increase in vitamin E concentrations in the blood plasma of calves in both experiments, the highest average level being recorded in 24 hours after administration (8.05, and/or 5.51 mumol/l; Tabs. I and IV). The level of total serum immunoglobulins was not influenced by vitamin E supplementation; this level remained below the physiological range of values in calves with peroral administration during the whole time of observation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interrelationships among liposoluble vitamins in ruminants

Plasma concentrations of vitamins A and E were examined in sheep, and a transitory decrease was observed after a single massive dose of vitamin D3 (5 X 10(6) IU) was administered orally or parenterally. Administration of a large dose of vitamin E to sheep decreased plasma retinol concentrations within 72 hours, but thereafter, the plasma retinol concentrations returned to near baseline values. Oral administration of a single pharmacologic dose of dl-alpha-tocopherol (5 g) to sheep caused a slow increase of this vitamin in the blood plasma. In cattle, a single IM administration of 3 liposoluble vitamins (A, D3, and E) at acceptable concentrations had no detectable influence on plasma alpha-tocopherol concentrations with the sampling intervals used. Plasma concentrations of alpha-tocopherol in these cattle showed a marked seasonal pattern; the concentrations increased from January to a peak in July, with a subsequent decrease in the fall. Also reported are estimates of inter- and intraindividual variation in plasma liposoluble vitamin concentrations.     

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)     

Bioavailability of oral penicillins in the horse: a comparison of pivampicillin and amoxicillin

The pharmacokinetics of ampicillin and amoxicillin following intravenous administration at a dose rate of 15 and 10 mg/kg respectively were studied in four healthy adult horses. Pharmacokinetics of pivampicillin and amoxicillin were studied after oral administration to four healthy adult horses. Pivampicillin, a prodrug of ampicillin, was administered orally to starved and fed horses at a dose rate of 19.9 mg/kg, which is equivalent on a molecular basis to 15 mg/kg ampicillin. Amoxicillin was administered orally to starved horses only, at a dose rate of 20 mg/kg. Ampicillin and amoxicillin concentrations in plasma, synovial fluid and urine were determined. Mean biological half-life of intravenously administered ampicillin and amoxicillin was 1.72 and 1.43 h respectively, whilst the distribution volume (Vss) appeared to be 0.180 and 0.192 1/kg. Orally administered pivampicillin and amoxicillin were rapidly absorbed. A maximum concentration in plasma of 3.80 micrograms/ml was reached 2 h after administration of pivampicillin to starved horses; in fed horses a maximum concentration of 5.12 micrograms/ml was reached 1 h after administration. After oral administration of amoxicillin a maximum concentration of 2.03 micrograms/ml was reached after 1 h. The (absolute) bioavailability of pivampicillin administered orally was 30.9% in starved horses and 35.9% in fed horses. The bioavailability of amoxicillin administered orally was 5.3% in starved horses.     

Effect of probenecid on disposition kinetics of ampicillin in horses.

The effect of an oral dose of probenecid on the disposition kinetics of ampicillin was determined in four horses. An intravenous bolus dose (10 mg/kg) of ampicillin sodium was administered to the horses on two occasions. On the first occasion the antibiotic was administered on its own, and on the second occasion it was administered one hour after an oral dose of 75 mg/kg probenecid. The plasma concentration of probenecid reached a mean (+/- se) maximum concentration (Cmax) of 188-6 +/- 19.3 micrograms/ml after 120.0 +/- 21.2 minutes and concentrations greater than 15 micrograms/ml were present 25 hours after it was administered. The disposition kinetics of ampicillin were altered by the presence of probenecid and as a result the antibiotic had a slower body clearance (ClB; 109.4 +/- 6.71 ml/kg hours compared with 208.9 +/- 26.2 ml/kg hours) a longer elimination half-life (t1/2 beta 1.198 hours compared with 0.701 hours) and consequently a larger area under the plasma concentration versus time curve (AUC 92.3 +/- 5.09 mg/ml hours compared with 35.95 +/- 3.45 mg/ml hours) when compared with animals to which ampicillin was administered alone. The ampicillin concentrations observed suggest that the dosing interval for horses may be increased from between six and eight hours to 12 hours when probenecid is administered in conjunction with the ampicillin.     

Comparison of pharmacokinetic variables for two injectable formulations of netobimin administered to calves

In a 4 x 4 crossover-design study, pharmacokinetic variables of 2 injectable formulations of netobimin (trisamine salt solution and zwitterion suspension) were compared after SC administration in calves at dosage of 12.5 mg/kg of body weight. Netobimin parent drug was rapidly absorbed, being detected between 0.25 and 12 hours after treatment, with maximal plasma drug concentration (Cmax) values of 2.20 +/- 1.03 micrograms/ml achieved at 0.75 +/- 0.19 hour (trisamine) and 1.37 +/- 0.59 micrograms/ml at 0.81 +/- 0.18 hour (zwitterion). Netobimin area under the plasma concentration-time curve (AUC) was 7.59 +/- 3.11 micrograms.h/ml (trisamine) and 6.98 +/- 1.60 micrograms.h/ml (zwitterion). Elimination half-life (t1/2 beta) was 2.59 +/- 0.63 hours (trisamine) and 3.57 +/- 1.45 hours (zwitterion). Albendazole was not detected at any time. Albendazole sulfoxide was detected from 4 hours up to 20 hours (trisamine) and from 6 hours up to 24 hours (zwitterion) after administration of the drug. The Cmax values were 0.48 +/- 0.16 micrograms/ml and 0.46 +/- 0.26 micrograms/ml for trisamine and zwitterion formulations, respectively, achieved at time to peak drug concentration (Tmax) values of 9.50 +/- 1.41 hours (trisamine) and 11.30 +/- 1.04 hours (zwitterion). Albendazole sulfoxide AUC was 3.86 +/- 1.04 micrograms.h/ml (trisamine) and 4.40 +/- 3.24 micrograms.h/ml (zwitterion); t1/2 beta was 3.05 +/- 0.75 hours (trisamine) and 3.90 +/- 1.44 hours (zwitterion). Albendazole sulfone was detected from 4 (trisamine) or 6 hours (zwitterion) to 24 hours after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative studies on bioavailability and tissue uptake of two intraruminally or intraperitoneally administered esters of alpha-tocopherol in sheep

An experiment was conducted to compare the bioavailability of dl-alpha-tocopherol acetate (TA) with that of dl-alpha-tocopherol nicotinate (TN) when administered to sheep, as a single dose, either into the rumen or the peritoneal cavity. A total of 16 sheep were used in a factorial design, with 4 sheep/treatment at the interaction level. In addition, 5 sheep that received no supplemental alpha-tocopherol, were euthanatized at the end of the trial to provide base-line data for tissue alpha-tocopherol concentrations. Curves were fitted to the plasma alpha-tocopherol concentration values, taken over 180 hours after administration of the esters. Availability of TA was greater than TN, as evidenced by the significantly higher curve parameter values (P less than 0.05) and tissue concentrations (P less than 0.05). Route of administration had a marked effect on availability of TA (P less than 0.001), but not of TN.     

Drug disposition and dosage determination of once daily administration of gentamicin sulfate in horses after abdominal surgery.

OBJECTIVE: To evaluate pharmacokinetics of once daily i.v. administration of gentamicin sulfate to adult horses that had abdominal surgery. DESIGN: Prospective study. ANIMALS: 28 adult horses that underwent abdominal surgery for colic. PROCEDURE: 14 horses were treated with each dosage of gentamicin (i.e., 6.6 or 4 mg/kg, i.v., q 24 h) and blood samples were collected for pharmacokinetic analysis. Plasma gentamicin concentrations were measured by use of a fluorescence polarization immunoassay. Pharmacokinetic analysis measured the elimination half-life, volume of distribution, and gentamicin total systemic clearance. Treatment outcome, CBC, and serum creatinine concentrations were recorded. RESULTS: 1 horse in the high-dosage group died. All other horses successfully recovered, and did not develop bacterial infection or have evidence of drug toxicosis resulting in renal injury. Mean pharmacokinetic variables for gentamicin administration at a high or low dosage (i.e., 6.6 or 4 mg/kg, i.v., q 24 h) were half-life of 1.47 and 1.61 hours, volume of distribution of 0.17 and 0.17 L/kg, and systemic clearance of 1.27 and 1.2 ml/kg/min, respectively. Mean serum creatinine concentration was 1.74 and 1.71 for the high and low dosages, respectively, and serum creatinine concentration was not correlated with gentamicin clearance. CONCLUSIONS AND CLINICAL RELEVANCE: Gentamicin administration at a dosage of 4 mg/kg, i.v., every 24 hours, will result in plasma concentrations that are adequate against susceptible bacteria with a minimum inhibitory concentration (MIC) of < or = 2.0 micrograms/ml. Gentamicin administration at a calculated dosage of 6.8 mg/kg, i.v., every 24 hours will result in optimum plasma concentrations against susceptible bacteria with a MIC of < or = 4.0 micrograms/ml.     

Prednisolone succinate and prednisolone acetate in cattle: pharmacokinetics and action on the adrenal gland

The pharmacokinetics of prednisolone were studied in a group of 6 cows given prednisolone 21-sodium succinate IV and IM (600 micrograms/kg of body weight expressed as prednisolone alcohol) and prednisolone acetate IM (600 micrograms/kg of body weight expressed as prednisolone alcohol). After IV administration of prednisolone 21-sodium succinate, the half-life of elimination was 3.6 +/- 1.177 hours. After IM administration of prednisolone 21-sodium succinate, absorption was rapid and complete. After IM administration of prednisolone acetate, absorption was very slow with an absorption half-life of 48 hours, but was still complete. Basal plasma hydrocortisone was about 7.5 ng/ml. After IV and IM administration of prednisolone 21-sodium succinate, plasma hydrocortisone returned to normal values within 48 hours. In contrast, after IM administration of prednisolone acetate, a long adrenal suppression lasting from 4 to 6 weeks was observed.     

Body fluid and endometrial concentrations of ketoconazole in mares after intravenous injection or repeated gavage

After single oral administration of ketoconazole (30 mg/kg bodyweight [bwt]) in 50 ml of corn syrup to a healthy mare, the drug was not detected in serum. Ketoconazole in 0.2 N HC1 was administered intragastrically to six healthy adult horses in five consecutive doses of 30 mg/kg bwt at 12 h intervals. Ketoconazole concentrations were measured in serum, synovial fluid, peritoneal fluid, cerebrospinal fluid (CSF), urine and endometrium. Mean peak serum ketoconazole concentration was 3.76 micrograms/ml at 1.5 to 2 h after intragastric administration. Mean peak synovial concentration was 0.87 micrograms/ml 3 h after the fifth dose. Similarly, mean peritoneal concentration peaked 3 h after the fifth dose at 1.62 micrograms/ml. Mean endometrial concentrations peaked at 2.73 micrograms/ml 2 h after the fifth dose. Ketoconazole was detected in the CSF of only one of the six mares at a concentration of 0.28 micrograms/ml 3 h after the fifth dose. The highest measured concentration of ketoconazole in urine was 6.15 micrograms/ml 2 h after the fifth dose. A single intravenous injection of ketoconazole (10 mg/kg bwt) was given to one of the six mares; the overall elimination rate constant was estimated at 0.22/h and bioavailability after oral administration was 23 per cent.     

Population distributions of phenylbutazone and oxyphenbutazone after oral and i.v. dosing in horses

Experiments to determine the residual plasma concentrations of phenylbutazone and its metabolites found in horses racing on a 'no-race day medication' or 24-h rule were carried out. One dosing schedule (oral-i.v.) consisted of 8.8 mg/kg (4 g/1000 lbs) orally for 3 days, followed by 4.4 mg/kg (2 g/1000 lbs) intravenously on day 4. A second schedule consisted of 4.4 mg/kg i.v. for 4 days. The experiments were carried out in Thoroughbred and Standardbred horses at pasture, half-bred horses at pasture, and in Thoroughbred horses in training. After administering the i.v. schedule for 4 days to Thoroughbred and Standardbred horses at pasture, the mean plasma concentrations of phenylbutazone increased from 0.77 microgram/ml on day 2 to 2.5 micrograms/ml on day 5. The shape of the frequency distribution of these populations was log-normal. These data are consistent with one horse in 1,000 yielding a plasma level of 8.07 micrograms/ml on day 5. After administration of the oral-i.v. schedule to Thoroughbred and Standardbred horses at pasture, the mean plasma concentrations of phenylbutazone were 3.4 micrograms/ml on day 2 and 3.5 micrograms/ml on day 5. The range on day 5 was from 1.4 to 8.98 micrograms/ml and the frequency distribution was log-normal. These data are consistent with one horse in 1000 having a plasma level of 15.8 micrograms/ml on day 5. In a final experiment, the oral dosing schedule was administered to 62 Thoroughbred horses in training. Plasma concentrations on day 5 in these horses averaged 5.3 micrograms/ml. The range was from 1.3 to 13.6 micrograms/ml and the frequency distribution was log-normal. Statistical projection of these values suggests that following this oral dosing schedule in racing horses about one horse in 1000 will yield a plasma level of 23.5 micrograms/ml of phenylbutazone 24 h after the last dose.     

Serum and tissue fluid norfloxacin concentrations after oral administration of the drug to healthy dogs

Norfloxacin, a 4-quinolone antibiotic, was administered orally to 4 healthy dogs at dosages of 11 and 22 mg/kg of body weight, every 12 hours for 4 days, with a 4-week interval between dosing regimens. Serum and tissue cage fluid (TCF) norfloxacin concentrations were measured at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after the first and seventh dose of each dosing regimen. When administered at a dosage of 11 mg/kg, the mean peak serum concentration (Cmax) was 1.0 microgram/ml at 1 hour, the time of mean peak concentration (Tmax) after the first dose. After the seventh dose, the Cmax was 1.4 micrograms/ml at Tmax of 1.5 hours. The Tmax for the TCF concentration was 5 hours, with Cmax of 0.3 microgram/ml and 0.7 microgram/ml after the first and seventh dose, respectively. When administered at a dosage of 22 mg/kg, the serum Tmax was 2 hours after the first dose, with Cmax of 2.8 micrograms/ml. After the seventh dose, the serum Tmax was 1.5 hours, with Cmax of 2.8 micrograms/ml. The Tmax for the TCF concentration was 5 hours after the first and seventh doses, with Cmax of 1.2 micrograms/ml and 1.6 micrograms/ml, respectively. After the seventh dose, the serum elimination half-life was 6.3 hours for a dosage of 11 mg/kg and was 6.7 hours for a dosage of 22 mg/kg. For serum concentration, the area under the curve from 0 to 12 hours (AUC0----12) was 8.77 micrograms.h/ml and 18.27 micrograms.h/ml for dosages of 11 mg/kg and 22 mg/kg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum and tissue cage fluid concentrations of ciprofloxacin after oral administration of the drug to healthy dogs

Ciprofloxacin, a fluoroquinolone antimicrobial agent, was administered orally to 4 healthy dogs at dosage of approximately 11 and 23 mg/kg of body weight, every 12 hours for 4 days, with a 4-week interval between dosing regimens. Serum and tissue cage fluid (TCF) concentrations of ciprofloxacin were measured after the first and seventh dose of each dosing regimen. The peak concentration was greatest in the serum after multiple doses of 23 mg/kg (mean +/- SEM; 5.68 +/- 0.54 micrograms/ml) and least in the TCF after a single dose of 11 mg/kg (0.43 +/- 0.54 micrograms/ml). The time to peak concentration was not influenced by multiple dosing or drug dose, but was longer for TCF (6.41 +/- 0.52 hour) than for serum (1.53 +/- 0.52 hour). Accumulation of ciprofloxacin was reflected by the area under the concentration curve from 0 to 12 hours after administration (AUC0----12). The AUC0----12 was greatest in the serum after multiple doses of 23 mg/kg (31.95 +/- 1.90 micrograms.h/ml) and least in the TCF after a single dose of 11 mg/kg (3.87 +/- 1.90 micrograms.h/ml). The elimination half-life was not influenced by multiple dosing or dose concentration, but was greater for TCF (14.59 +/- 1.91 hours) than for serum (5.14 +/- 1.91 hours). The percentage of TCF penetration (AUCTCF/AUCserum) was greater after multiple doses (95.76 +/- 6.79%) than after a single dose (55.55 +/- 6.79%) and was not different between doses of 11 and 23 mg/kg. Both dosing regimens of ciprofloxacin resulted in continuous serum and TCF concentrations greater than 90% of the minimal inhibitory concentration for the aerobic and facultative anaerobic clinical isolates tested, including Pseudomonas aeruginosa.     

Evaluating the antioxidant status of weanling pigs fed dietary vitamins A and E

Two experiments evaluated the relationship of vitamin E (source and level) and vitamin A (level) on the apparent absorption and retention of both vitamins in weaned pigs. Both experiments used a combined total of 460 crossbred pigs ([Yorkshire x Landrace] x Duroc), housed in elevated 1.2- x 1.2-m crates containing five pigs per pen. Experiment 1 was a 2 x 2 x 2 factorial arrangement of treatments in a randomized complete block design conducted in seven replicates. Levels of vitamin A (2,200 or 13,200 IU/kg), vitamin E (15 or 90 IU/kg), and two vitamin E sources (D-alpha-tocopheryl acetate [D-TAc] or DL-alpha-tocopheryl acetate [DL-TAc]) were evaluated over a 35-d period. Vitamin A or E levels and the two vitamin E sources did not affect pig performances to 20 kg BW. Serum retinol and alpha-tocopherol concentrations increased (P < 0.01) as the dietary level of each vitamin increased. Serum alpha-tocopherol declined as dietary vitamin E level increased when vitamin A level increased resulting in an interaction (P < 0.05). Serum alpha-tocopherol concentrations were higher (P < 0.05) at 35-d postweaning when D-TAc was the vitamin E source. Experiment 2 was a 3 x 2 factorial arrangement of treatments conducted in six replicates. Three levels of vitamin A (2,200, 13,200, or 26,400 IU/ kg) and two sources of vitamin E (D-TAc or DL-TAc) each provided at 40 IU/kg diet were evaluated over a 35-d period. Pig performances to 35-d postweaning were not affected by the dietary variables. Serum alpha-tocopherol (P < 0.01) and retinol (P < 0.05) concentrations increased as their respective vitamin level increased. Serum (P < 0.05) and liver (P < 0.01) alpha-tocopherol concentrations both declined as dietary vitamin A levels increased resulting in interaction responses. Serum alpha-tocopherol concentration was higher (P < 0.05) at 35-d postweaning when d-TAc was the vitamin E source. Dietary vitamin E sources had no effect on serum or liver retinol concentrations. These results demonstrated that both supplemental vitamin A and vitamin E increased in the blood as their dietary levels increased. However, as dietary vitamin A level increased, serum and liver alpha-tocopherol concentrations declined, suggesting a reduced absorption and retention of alpha-tocopherol when weaned pigs were fed high dietary vitamin A levels.     

An evaluation of natural (RRR-alpha-tocopheryl acetate) and synthetic (all-rac-alpha-tocopheryl acetate) vitamin E fortification in the diet or drinking water of weanling pigs

Three experiments conducted with weanling pigs evaluated the effects of vitamin E added to the drinking water or diet on plasma and tissue alpha-tocopherol concentrations. When natural or synthetic vitamin E was used, it was added at an IU-equivalent basis, but natural vitamin E was 73.5% (mg basis) of the synthetic vitamin E. Experiment 1 used 18-d-old weanling pigs (n = 120) in a 3 x 2 factorial arrangement of treatments in a randomized complete block design with 4 replicates. The first factor evaluated the dietary levels of natural vitamin E (RRR-alpha-tocopheryl acetate) added at 0, 50, or 300 IU/kg, whereas the second factor was the natural vitamin E added to the drinking water at 0 or 100 IU/L. Pigs were bled at periodic intervals, and 1 pig per pen was killed at the end of the 21-d trial and tissues (liver, heart, lung, and loin) were collected for alpha-tocopherol analysis. When vitamin E was not added to the diet or water, plasma alpha-tocopherol declined over the 21-d period. Although there were some interactions (P < 0.01), tissue and plasma alpha-tocopherol concentrations increased linearly when vitamin E was added to the diet or water. Experiment 2 was a 3 x 2 factorial in a randomized complete block design with 4 replicates. A total of 96 pigs weaned at 18 d of age, with an initial BW of 6.2 kg, were fed a nonvitamin E fortified diet, but natural or synthetic (all-rac-alpha-tocopheryl acetate) vitamin E was added to their drinking water at 50, 100, or 150 IU/L. Pigs were bled at 0, 3, 7, 10, 14, and 21 d postweaning, with tissues (liver, lung, heart, and loin) collected for alpha-tocopherol analysis at d 21. The results indicated that plasma alpha-tocopherol concentrations increased (P < 0.01) as vitamin E increased, with greater tissue alpha-tocopherol concentrations (P < 0.01) when natural vitamin E was provided. Experiment 3 was conducted in 2 replicates, but pigs (n = 60) were not provided vitamin E in the diet or water for 7 d postweaning, and then natural or synthetic vitamin E was added to the drinking water as in Exp. 2 (50, 100, or 150 IU/L). Pigs were bled at 0, 2, 4, 6, 8, 10, and 24 h after being provided vitamin E to evaluate the absorption from each vitamin E source and level. Plasma alpha-tocopherol increased quadratically (P < 0.01) and plateaued at 8 to 10 h for each treatment group. These results indicate that adding vitamin E to the pig's water supply at weaning was more effective in increasing plasma alpha-tocopherol than when it was added to the diet during the initial 14 d postweaning, and that natural vitamin E was a superior source compared with synthetic vitamin E.     

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.