Pharmacokinetics of norfloxacin and its N-desethyl- and oxo-metabolites in broiler chickens.

Norfloxacin was given to 2 groups of chickens (8 chickens/group) at a dosage of 8 mg/kg of body weight, IV and orally. For 24 hours, plasma concentration was monitored serially after each administration. Another group of chickens (n = 30) was given 8 mg of norfloxacin/kg orally every 24 hours for 4 days, and plasma and tissue concentrations of norfloxacin and its major metabolites desethylenenorfloxacin and oxonorfloxacin were determined serially after the last administration of the drug. Plasma and tissue concentrations of norfloxacin, desethylenenorfloxacin, and oxonorfloxacin were measured by use of high-performance liquid chromatography. Pharmacokinetic variables were calculated, using a 2-compartment open model. For norfloxacin, the elimination half-life (t1/2 beta) and the mean +/- SEM residence time for plasma were 12.8 +/- 0.59 and 15.05 +/- 0.81 hours, respectively, after oral administration and 8.0 +/- 0.3 and 8.71 +/- 0.23 hours, respectively, after IV administration. After single oral administration, norfloxacin was absorbed rapidly, with Tmax of 0.22 +/- 0.02 hour. Maximal plasma concentration was 2.89 +/- 0.20 microgram/ml. Oral bioavailability of norfloxacin was found to be 57.0 +/- 2.4%. In chickens, norfloxacin was mainly converted to desethylenenorfloxacin and oxonorfloxacin. Norfloxacin parent drug and its 2 major metabolites were widely distributed in tissues. Considerable tissue concentrations of norfloxacin, desethylenenorfloxacin, and oxonorfloxacin were found when norfloxacin was administered orally (8 mg/kg on 4 successive days). The concentration of the parent fluoroquinolone in fat, kidneys, and liver was 0.05 micrograms/g on day 12 after the end of dosing.     

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 skin concentrations after multiple-dose oral administration of trimethoprim-sulfadiazine in dogs.

Six healthy adult mixed breed dogs were each given 5 oral doses of trimethoprim (TMP)/sulfadiazine (SDZ) at 2 dosage regimens: 5 mg of TMP/kg of body weight and 25 mg of SDZ/kg every 24 hours (experiment 1) and every 12 hours (experiment 2). Serum and skin concentrations of each drug were measured serially throughout each experiment and mean serum concentrations of TMP and SDZ were determined for each drug for 24 hours (experiment 1) and 12 hours (experiment 2) after the last dose was given. In experiment 1, mean serum TMP concentration was 0.67 +/- 0.02 micrograms/ml, and mean skin TMP concentration was 1.54 +/- 0.40 micrograms/g. Mean serum SDZ concentration was 51.1 +/- 12.2 micrograms/ml and mean skin SDZ concentration was 59.3 +/- 9.8 micrograms/g. In experiment 2, mean serum TMP concentration was 1.24 +/- 0.35 micrograms/ml and mean skin TMP concentration was 3.03 +/- 0.54 micrograms/g. Mean serum SDZ concentration was 51.6 +/- 9.3 micrograms/ml and mean skin SDZ concentration was 71.1 +/- 8.2 micrograms/g. After the 5th oral dose in both experiments, mean concentration of TMP and SDZ in serum and skin exceeded reported minimal inhibitory concentrations of TMP/SDZ (less than or equal to 0.25/4.75 micrograms/ml) for coagulase-positive Staphylococcus sp. It was concluded that therapeutically effective concentrations in serum and skin were achieved and maintained when using the manufacturer's recommended dosage of 30 mg of TMP/SDZ/kg (5 mg of TMP/kg and 25 mg of SDZ/kg) every 24 hours.     

Pharmacokinetics and tissue residues of pefloxacin and its metabolite norfloxacin in broiler chickens

1. The pharmacokinetics of pefloxacin and its active metabolite norfloxacin were investigated in chickens after a single oral administration of pefloxacin at a dosage of 10 mg/kg. To characterise the residue pattern, another group of chickens was given 10 mg of pefloxacin/kg body once daily for 4 d by oral route; the tissue concentrations of pefloxacin and norfloxacin were determined at 1, 5 and 10 d after the last administration of the drug. 2. The concentrations of pefloxacin and norfloxacin in plasma and tissues were determined by HPLC assay. The limit of detection for pefloxacin and norfloxacin was 0.03 microg/ml in plasma or microg/g in tissue. 3. The plasma concentration-time data for pefloxacin and norfloxacin were characteristic of a one-compartment open model. The elimination half-life, maximum plasma drug concentration, time to reach maximum plasma drug concentration and mean residence time of pefloxacin were 8.74 +/- 1.48 h, 3.78 +/- 0.23 microg/ml, 3.33 +/- 0.21 h and 14.32 +/- 1.94 h, respectively, whereas the respective values of these variables for norfloxacin were 5.66 +/- 0.81 h, 0.80 +/- 0.07 microg/ml, 3.67 +/- 0.21 h and 14.44 +/- 0.97 h. 4. Pefloxacin was metabolised to norfloxacin to the extent of 22%. 5. The concentrations of pefloxacin (microg/g) 24 h after the fourth dose of the drug declined in the following order: liver (3.20 +/- 0.40) > muscle (1.42 +/- 0.18) > kidney (0.69 +/- 0.04) > skin and fat (0.06 +/- 0.02). Norfloxacin was also detectable in all the tissues analysed except muscle. No drug and/or its metabolite was detectable in tissues except skin and fat 5 d after the last administration. The concentrations of pefloxacin and norfloxacin in skin and fat 10 d after the last dose of pefloxacin were 0.04 +/- 0.02 and 0.03 +/- 0.01 microg/g, respectively.     

Serum concentrations of cefepime (BMY-28142), a broad-spectrum cephalosporin, in dogs.

Serum concentrations of cefepime (BMY-28142) were determined for four dosing regimes, 10 mg/kg or 20 mg/kg, given as single subcutaneous (SC) or intramuscular injections (IM) to dogs. Serial serum samples were analyzed for the presence of cefepime by high-performance liquid chromatography. In experiment 1, the overall mean (+/- SEM) serum concentration (for a 12-hour period) after a dose of 20 mg/kg for SC and IM routes (4.9 +/- 0.74 micrograms/ml and 5.5 +/- 0.63 micrograms/ml, respectively) was twice that for the 10 mg/kg dose given either SC or IM (2.2 +/- 0.31 micrograms/ml and 2.8 +/- 0.47 micrograms/ml, respectively). There was no significant difference (p greater than 0.05) in mean serum concentrations for SC and IM routes of administration at the same dosage. In subsequent experiments, 5 doses of cefepime (20 mg/kg) were administered IM at 12-hour (experiment 2) or 24-hour (experiment 3) intervals. The mean (+/- SEM) peak serum concentration was 12.1 +/- 1.59 micrograms/ml, 2 hours after the 2nd injection in experiment 2. In experiment 3, the mean (+/- SEM) peak serum concentration was 10.9 +/- 1.34 micrograms/ml, 4 hours after the 1st injection. Mean trough concentrations in experiment 2 were greater than or equal to 0.5 microgram/ml and less than or equal to 0.5 in experiment 3. Multiple IM doses produced transient edema at the injection site and mild lameness in all dogs. Cefepime was highly active against single canine isolates of Staphylococcus intermedius, Pseudomonas aeruginosa and Escherichia coli, with minimum inhibitory concentrations of 0.125 microgram/ml, 1 microgram/ml and 0.3 microgram/ml, respectively.     

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.     

Pharmacokinetics of single doses of phenobarbital given intravenously and orally to dogs

Pharmacokinetics of phenobarbital was studied in 10 healthy dogs after single IV or oral administration. Phenobarbital sodium was administered IV to 5 dogs in group A (5.5 mg/kg of body weight) and 5 dogs in group B (15 mg/kg). Serial venous blood samples (n = 21) were collected from each dog before (base line) and after the administration of phenobarbital sodium for pharmacokinetic evaluation. After a 30-day resting period, 3 dogs in group A and 3 in group B were randomly selected and used for an IV crossover treatment. The IV treatment mean half-life of phenobarbital sodium was 92.6 +/- 23.7 and 72.3 +/- 15.5 hours, whereas mean total clearance was 5.60 +/- 2.31 and 6.66 +/- 0.78 ml/hr/kg for doses of 5 and 15 mg/kg, respectively. The mean residence time was 124 +/- 34 hours and 106 +/- 23 hours for the 5.5 and 15 mg/kg, IV doses, respectively. Significant differences (P greater than 0.05) were not observed in pharmacokinetic parameters between the 2-dose study. After a 35-day resting period, dogs in groups A and B were treated as described for the single IV treatment, except that they were given a phenobarbital tablet orally. Serial venous blood samples (n = 24) were collected before (base line) and after the administration of phenobarbital. Mean bioavailability was 88.1 +/- 12.4% and 96.8 +/- 9.0%, half life of absorption was 0.263 +/- 0.185 and 0.353 +/- 0.443 hour, and lag time was 0.611 +/- 0.683 and 0.741 +/- 0.554 hour for groups A and B, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics and tissue residues of josamycin in fowls.

Josamycin is a macrolide antibiotic which is produced by fermentation of cultures of Streptomyces narbonensis. It was once administrated (18 mg/kg b. wt.) in fowls via intravenous, oral and intramuscular routes for determination of blood concentration, kinetic behaviour and bioavailability. Following a single intravenous injection, the blood concentration-time-curve indicated a two compartments open model with an elimination half life value (t1/2 beta) of 1.83 +/- 0.06 hours. Both oral and intramuscular routes showed higher values, i.e. 2.33 +/- 0.13 and 2.85 +/- 0.17 hours. The lower apparent volume of distribution of Josamycin in fowls than one liter/kg elucidate higher distribution in blood than in tissues. Systemic bioavailability after both oral and intramuscular administration, i.e. 33.88 +/- 2.4 and 27.28 +/- 1.46% respectively, showed lower absorption from site of i.m. application. Josamycin was administered (18 mg/kg b. wt.) intramuscularly and orally once daily for 5 consecutive days. The drug peaked in serum 1 hour (intramuscular) and 2 hours (orally) after each dose. The recorded results revealed that serum level of Josamycin was higher after oral application (29.98 +/- 1.92 micrograms/ml) than after i.m. application. The drug persisted in the lung tissues and fat for 72 hours after administration and disappeared from all body tissues 96 hours after the last dose of repeated administration.     

Pharmacokinetics and interactions of digoxin with phenobarbital in dogs

In one experiment, 5 dogs were administered digoxin (0.022 mg/kg of body weight, IV), were rested for 2 weeks, were then given phenobarbital (13.2 mg/kg orally) for 14 days, and then were given digoxin again (0.022 mg/kg, IV). Comparing prephenobarbital (control) digoxin half-lives of 42.4 +/- 8.8 hours and postphenobarbital digoxin half-lives of 18.0 +/- 2.2 hours, the half-life was significantly (P less than 0.05) decreased after phenobarbital administration. Clearance was increased by 84%, and the volume of distribution given was decreased by 34%. In a second experiment, 5 dogs were given digoxin (0.022 mg/kg, orally) daily for 11 days, and the digoxin kinetics were evaluated after the last dosing. The dogs were then rested and given phenobarbital (13.2 mg/kg, orally) once daily for 14 days and digoxin (0.022 mg/kg) once daily for 11 days, and the pharmacokinetics of digoxin was determined on the last day of dosing. Significant differences in steady-state serum concentrations and the pharmacokinetics of digoxin were not found between the control and phenobarbital phases of the experiment. Mean (+/- SD) half-lives of digoxin were 29.0 +/- 7.2 hours before phenobarbital treatment (control) and were 34.8 +/- 7.2 hours after phenobarbital treatment. In comparing results of the single-dose experiment vs the oral multiple-dose experiment, dogs had shorter half-lives for digoxin after multiple dosing. Therefore, if phenobarbital and digoxin are to be chronically coadministered orally, an adjustment in the digoxin dose is not necessary.     

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 and bioavailability of spiramycin in pigs.

The pharmacokinetics of spiramycin in pigs were investigated after intravenous and oral administration. The potential therapeutically effective blood level was established after a single administration and examined in a subsidiary five day study. The rapid intravenous injection of 25 mg spiramycin/kg bodyweight produced marked salivation in all the test animals. The elimination half-life (2.3 +/- 1.2 hours) was relatively short, in accordance with the total body clearance rate (27.3 +/- 10.1 ml/minute/kg). The high volume of distribution (5.2 +/- 2.2 litres/kg) was due to the accumulation of the drug in the body tissues. The maximum plasma concentration (4.1 +/- 1.7 micrograms/ml) after oral administration of 85 to 100 mg spiramycin/kg bodyweight was reached after 3.7 +/- 0.8 hours and the half-life of the elimination phase was 6.0 +/- 2.4 hours. The oral bioavailability was 45.4 +/- 23.4 per cent. Ad libitum feeding of a diet containing 2550 mg spiramycin/kg produced a steady state concentration of 0.96 +/- 0.27 micrograms/ml. This plasma concentration would provide a potentially therapeutically effective blood concentration against Mycoplasma species, Streptococcus species and Staphylococcus species.     

Flunixin pharmacokinetics and serum thromboxane inhibition in the dog

Flunixin meglumine administered orally to beagle dogs at doses of 0.55, 1.10 or 1.65 mg/kg bodyweight was rapidly absorbed to produce maximum mean plasma concentrations of 2.40 +/- 0.70, 4.57 +/- 1.12 and 7.42 +/- 2.07 micrograms/ml, respectively. Thereafter, the plasma concentrations of flunixin fell rapidly to values less than 0.10 micrograms/ml from 24 hours after drug administration at all dosage levels. The maximum mean inhibition of serum thromboxane B2 was 91.5 per cent after the lowest dose of flunixin and 98.8 per cent for both the intermediate and high dose rates. At plasma concentrations of flunixin above 2 micrograms/ml there was more than 90 per cent inhibition of thromboxane.     

Serum disposition of exogenous progesterone after intramuscular administration in bitches

Progesterone was administered IM to 6 adult anestrous bitches at a dosage of 2 mg/kg of body weight. Serum progesterone concentrations were measured prior to progesterone administration and for 72 hours thereafter. The serum progesterone concentration time data were analyzed by use of a pharmacokinetics modeling computer program. The mean (+/- SD) peak serum progesterone concentration (34.3 +/- 7.8 ng/ml) was reached at 1.8 +/- 0.2 hours after progesterone administration. The mean serum progesterone concentration was 6.9 +/- 1.4 ng/ml at 24 hours and 2.0 +/- 0.4 ng/ml at 48 hours after progesterone administration. By 72 hours after administration, mean serum progesterone concentration was 0.9 +/- 0.2 ng/ml, which was comparable to serum progesterone concentrations prior to injection. The mean half-life of the absorption phase was 0.5 hours (range, 0.3 to 0.7 hours). The mean half-life of elimination was 12.1 hours (range, 9.5 to 13.8 hours). By analysis of the data, it was established that a dosage of 3 mg/kg, when the hormone was given IM to dogs once a day, would maintain serum progesterone concentration greater than 10 ng/ml.     

Single- and multiple-dose pharmacokinetics of intravenously administered vancomycin in dogs

Vancomycin was administered IV to healthy adult female dogs at a dosage of 15 mg/kg of body weight every 12 hours for 10 days. Pharmacokinetic values were determined after the first and last doses. The disposition of vancomycin was not altered by multiple dosing, and little accumulation attributable to multiple dosing was observed. Serum vancomycin concentration after the first and last dose were described, using a 2-compartment open model with first-order elimination. The distribution and elimination half-lives after the single dose were 15.4 +/- 2.7 minutes and 137 +/- 21.8 minutes (geometric mean +/- pseudo-SD), respectively; whereas the distribution and elimination half-lives after the last dose were 11.3 +/- 2.61 minutes and 104 +/- 11.2 minutes, respectively. The mean (+/- SD) area-derived volume of distribution was 396 +/- 156 ml/kg and 382 +/- 160 ml/kg after the first and last dose, respectively. Serum vancomycin clearance was 2.13 +/- 0.35 ml/min/kg and 2.49 +/- 0.79 ml/min/kg after the first and last dose, respectively, and 25 to 49% of the total dose of vancomycin was recovered in the urine in the first 24 hours after the single dose administered IV. Mean serum vancomycin concentration reached 101.8 +/- 30.6 micrograms/ml and 99.7 +/- 28.0 micrograms/ml at 5 minutes after a single dose and the last of the multiple doses, respectively, and decreased to 0.94 +/- 0.58 microgram/ml and 1.51 +/- 1.44 micrograms/ml, respectively, at 12 hours after administration. The side effects that accompany vancomycin treatment in human beings were not observed in the dogs; all remained healthy through the end of the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of probenecid administration on cephapirin pharmacokinetics and concentrations in mares

Cephapirin (20 mg/kg of body weight, IV) was administered before and after 3 doses of probenecid (25, 50, or 75 mg/kg, intragastrically, at 12-hour intervals) to 2 mares. Clearance and apparent volume of distribution, based on area under the curve, were negatively correlated with probenecid dose. Clearance of cephapirin was decreased by approximately 50% by administration of 50 mg of probenecid/kg. Serum, synovial fluid, peritoneal fluid, CSF, urinary, and endometrial concentrations of cephapirin were determined after 5 doses of cephapirin (20 mg/kg, IM, at 12-hour intervals) without and with concurrently administered probenecid (50 mg/kg, intragastrically) to 6 mares, including the 2 mares given cephapirin, IV. Highest mean serum cephapirin concentrations were 16.1 +/- 2.16 micrograms/ml at 0.5 hour after the 5th cephapirin dose [postinjection (initial) hour (PIH) 48.5] in mares not given probenecid and 23.7 +/- 1.30 micrograms/ml at 1.5 hours after the 5th cephapirin dose (PIH 49.5) in mares given probenecid. Mean peak peritoneal fluid and synovial fluid cephapirin concentrations were 6.2 +/- 0.57 micrograms/ml and 6.6 +/- 0.58 micrograms/ml, respectively, without probenecid administration and 12.3 +/- 0.46 micrograms/ml and 10 +/- 0.78 micrograms/ml, respectively, with concurrent probenecid administration. Mean trough cephapirin concentrations for peritoneal and synovial fluids in mares given probenecid were 2 to 3 times higher than trough concentrations in mares not given probenecid. Overall mean cephapirin concentrations were significantly higher for serum, peritoneal fluid, synovial fluid, and endometrium when probenecid was administered concurrently with cephapirin (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of probenecid and the effect of oral probenecid administration on the pharmacokinetics of cefazolin in mares

The pharmacokinetics and bioavailability of probenecid given IV and orally at the dosage level of 10 mg/kg of body weight to mares were investigated. Probenecid given IV was characterized by a rapid disposition phase with a mean half-life of 14.0 minutes and a subsequent slower elimination phase with a mean half-life of 87.8 minutes in 5 of 6 mares. In the remaining mare, a rapid disposition phase was not observed, and the half-life of the elimination phase was slower (172 minutes). The mean residence time of probenecid averaged 116 minutes for all 6 mares and 89.2 minutes for the 5 mares with biphasic disposition. The total plasma clearance of probenecid averaged 1.18 +/- 0.49 ml/min/kg, whereas renal clearance accounted for 42.6 +/- 9.3% of the total clearance. The steady-state volume of distribution of probenecid averaged 116 +/- 28.2 ml/kg. Plasma protein binding of probenecid was extensive, with 99.9% of the drug bound at plasma probenecid concentrations of 10 micrograms/ml. The maximum plasma probenecid concentration after 10 mg/kg orally averaged nearly 30 micrograms/ml. The half-life of probenecid after oral administration was approximately 120 minutes. Oral bioavailability was good with greater than 90% of the dose absorbed. The effect of probenecid on tubular secretion of organic anions was evaluated by determining the pharmacokinetics of IV cefazolin (11 mg/kg) administered alone and 15 minutes after probenecid (10 mg/kg orally). Treatment with probenecid did not affect pharmacokinetic values of cefazolin. This failure of probenecid to alter the pharmacokinetics of cefazolin may be caused by insufficient plasma probenecid concentrations after the oral dose.     

Pharmacokinetics and body fluid and endometrial concentrations of cefoxitin in mares

Four healthy adult mares were each given a single injection of sodium cefoxitin (20 mg/kg of body weight, IV), and serum cefoxitin concentrations were measured serially during a 6-hour period. The mean elimination rate constant was 1.08/hour and the elimination half-life was 0.82 hour. The apparent volume of distribution (at steady state) and the clearance of the drug were estimated at 0.12 L/kg and 259 ml/hr/kg, respectively. Each mare and 2 additional mares were then given 4 consecutive IM injections of sodium cefoxitin (400 mg/ml) at a dosage of 20 mg/kg. Cefoxitin concentrations in serum, synovial fluid, peritoneal fluid, CSF, urine, and endometrium were measured serially. After IM administration, the highest mean serum concentration was 23.1 micrograms/ml 30 minutes after the 2nd injection. The highest mean synovial concentration was 11.4 micrograms/ml 1 hour after the 4th injection. The highest mean peritoneal concentration was 10.4 micrograms/ml 2 hours after the 4th injection. The highest mean endometrial concentration was 4.5 micrograms/g 4 hours after the 4th injection. Mean urine concentrations reached 11,645 micrograms/ml. Cefoxitin did not readily penetrate the CSF. Bioavailability of cefoxitin given IM was 65% to 89% (mean +/- SEM = 77% +/- 5.9%). One of the 6 mares developed acute laminitis during the IM experiment.     

Pharmacokinetics of gentamicin at steady-state in ponies: serum, urine, and endometrial concentrations

Gentamicin (GT) was administered IM to 6 healthy mature mare ponies at a dosage of 5 mg/kg of body weight every 8 hours for 7 consecutive days (total, 21 doses). Two venous blood samples were collected before (trough) and at 1 hour (peak) after the 5th, 10th, 14th, and 19th doses. An endometrial biopsy was done of each mare on days 4 and 7. On the 7th day, just before the 21st administration of GT, base-line blood samples were collected, and 22 blood samples were collected over a period of 48 hours after GT was given. The mares were catheterized on the 7th day, and urine was collected for 24 hours. Serum, urine, and endometrial GT concentrations were determined by a radioimmunoassay technique (sensitivity of 0.3 micrograms/ml of serum). Serum GT concentration data obtained from the terminal phase were best fitted by a 1-compartment open model with a biological half-life of 2.13 +/- 0.43 hours. Total body clearance and renal clearance were 1.69 +/- 0.41 and 1.40 +/- 0.26 ml/min/kg, respectively. Mean endometrial concentrations on day 4 and day 7 were 5.02 +/- 3.3 and 12.75 +/- 1.6 micrograms/g. To achieve mean serum GT concentrations (micrograms/ml) at steady state of 6.47 +/- 1.51, a maximum steady-state concentration of 12.74 +/- 1.60, and a minimum steady-state concentration of 1.43 +/- 0.57, a dosage of 5 mg/kg every 8 hours is recommended. Serum urea nitrogen, serum creatinine, and the fractional clearance of sodium sulfanilate were determined before and after GT treatment. Renal function remained within the base-line range during 7 days of GT administration.     

Plasma concentrations of oxytetracycline in swine after administration of the drug intramuscularly and orally in feed

Four pigs were used in a 2 X 2 crossover study to determine plasma oxytetracycline (OTC) concentration and OTC pharmacokinetic variables after IM administration of 2 OTC preparations--long acting OTC and a 100-mg of OTC/ml solution (OTC-LA and OTC-100, respectively)--at a dosage of 20 mg/kg of body weight. In a second study, 3 additional pigs were given ad libitum access to feed containing pure OTC (0.55 g/kg of feed). The mean (+/- SD) peak plasma OTC concentration after OTC-LA administration was 6.0 +/- 2.2 micrograms/ml at 30 minutes; the mean peak plasma OTC concentration after OTC-100 administration was 6.7 +/- 3.4 micrograms/ml at 90 minutes. Mean plasma OTC concentration after oral OTC administration in feed peaked at 0.4 micrograms/ml 48 hours after access to OTC-medicated feed and decreased to 0.25 micrograms/ml by the end of that study. Mean plasma OTC concentration was maintained at greater than 0.5 micrograms/ml for less than 48 hours after OTC-LA administration and for less than 36 hours after OTC-100 administration. Mean plasma OTC concentration decreased to less than 0.2 micrograms/ml by 72 hours after IM administration of either product. Calculation of area under the plasma OTC concentration-time curve (AUC) did not reveal significant difference between the 2 OTC formulations. There also was not significant difference (between OTC-LA and OTC-100) in the value of the disappearance rate constant after administration of either OTC formulation. The data did not indicate significant pharmacologic advantage of OTC-LA, compared with OTC-100, when either formulation was administered IM at a dosage of 20 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of metronidazole and its concentration in body fluids and endometrial tissues of mares.

Serum concentrations of metronidazole were determined in 6 healthy adult mares after a single IV injection of metronidazole (15 mg/kg of body weight). The mean elimination rate (K) was 0.23 h-1, and the mean elimination half-life (t1/2) was 3.1 hours. The apparent volume of distribution at steady state was 0.69 L/kg, and the clearance was 168 ml/h/kg. Each mare was then given a loading dose (15 mg/kg) of metronidazole at time 0, followed by 4 maintenance doses (7.5 mg/kg, q 6 h) by nasogastric tube. Metronidazole concentrations were measured in serial samples of serum, synovia, peritoneal fluid, and urine. Metronidazole concentrations in CSF and endometrial tissues were measured after the fourth maintenance dose. The highest mean concentration in serum was 13.9 +/- 2.18 micrograms/ml at 40 minutes after the loading dose (time 0). The highest mean synovial and peritoneal fluid concentrations were 8.9 +/- 1.31 micrograms/ml and 12.8 +/- 3.21 micrograms/ml, respectively, 2 hours after the loading dose. The lowest mean trough concentration in urine was 32 micrograms/ml. Mean concentration of metronidazole in CSF was 4.3 +/- 2.51 micrograms/ml and the mean concentration in endometrial tissues was 0.9 +/- 0.48 micrograms/g at 3 hours after the fourth maintenance dose. Two mares hospitalized for treatment of bacterial pleuropneumonia were given metronidazole (15.0 mg/kg, PO, initially then 7.5 mg/kg, PO, q 6 h), while concurrently receiving gentamicin, potassium penicillin, and flunixin meglumine IV. Metronidazole pharmacokinetics and serum concentrations in the sick mares were similar to those obtained in the healthy mares.