Ampicillin trihydrate in foals: serum concentrations and clearance after a single oral dose

Five foals from two to three days old were given a single oral dose of ampicillin trihydrate (20 mg/kg bodyweight [bwt]). Serum ampicillin concentrations were measured serially over a 24 h period. The study was repeated in the same foals at 16 to 21 days old. The mean peak serum ampicillin concentration at two to three days old was 5.0 micrograms/ml at 1 h after treatment; the mean peak serum concentration at 16 to 21 days old was 2.7 micrograms/ml at 2 h. The concentrations steadily declined and ampicillin was not detected in the serum from any of the foals by 24 h. Serum clearance averaged 17.7 ml/min/kg at two to three days and 35.8 ml/min/kg at 16 to 21 days.     

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)     

Concentrations of gentamicin in serum, milk, urine, endometrium, and skeletal muscle of cows after repeated intrauterine injections

Healthy mature cows (n = 6) were injected intrauterinally (IU) with gentamicin (50 ml of a 5% injectable solution) daily for 3 consecutive days. Venous blood and milk samples were collected at postinjection (initial) hours (PIH) 1, 3, 6, 9, 12, 24, 28, 31, 34, 37, 48, 51, 54, 57, 60, and 71, and endometrial biopsies were performed at PIH 6, 25, 48, 73, 95, and 119. Skeletal muscle biopsy samples were taken at PIH 25 and 73, and urine was collected every 1 or 2 hours during 12 consecutive hours after the first IU injection. Serum, milk, urine, and tissue concentrations of gentamicin were measured by radioimmunoassay. The highest mean serum concentration of gentamicin occurred during the 3 hours after each injection (2.49 +/- 1.46, 6.60 +/- 5.47, and 4.98 +/- 2.70 micrograms/ml). The mean peak concentration of gentamicin in milk occurred 3 to 6 hours after each injection. Mean peak urine concentration of gentamicin (256.8 +/- 127.9 micrograms/ml) was measured at PIH 6. The mean percentage of the first dose of gentamicin excreted in the urine within 12 hours was 14.78 +/- 3.56. The highest concentration of gentamicin in endometrial tissue (639.16 +/- 307.22 micrograms/g) was measured at PIH 6, decreasing to 9.64 +/- 3.55 micrograms/g before the next IU dose. Gentamicin was still detectable in endometrial tissue (0.86 +/- 0.43 microgram/g) 71 hours after the 3rd (last) IU injection.     

Serum concentrations of etorphine in juvenile African elephants

Eleven juvenile African elephants were given etorphine hydrochloride (2.19 +/- 0.11 micrograms/kg of body weight; mean +/- SD) as a single IM injection; 3 elephants were given additional etorphine (0.42 +/- 0.09 micrograms/kg) IV. After immobilization, each elephant was maintained in lateral recumbency by administration of a 0.5% halothane/oxygen mixture or by administration of multiple IV injections of etorphine. At postinjection hours 0.25 and 0.5 and at 30-minute intervals thereafter, blood samples were collected via an auricular artery, and serum concentrations of etorphine were determined by use of radioimmunoassay. The highest mean serum concentration of etorphine in 6 elephants given a single IM injection and subsequently maintained on halothane and oxygen was 1.62 +/- 0.97 ng/ml at postinjection hours 0.5; thereafter, the mean serum concentration decreased steadily. In 4 elephants maintained in lateral recumbency with multiple IV administrations of etorphine, a correlation was not found between the time to develop initial signs of arousal and serum concentrations of etorphine before arousal. After administration of the initial immobilizing dose of etorphine, the interval between successive IV administrations of etorphine decreased.     

Gentamicin tissue concentrations in equine small intestine and large colon

Gentamicin sulfate (2.2 mg/kg of body weight, IV) was given to anesthetized horses. Jejunal and large colon tissue samples (1 g), serum, and urine were collected over a 4-hour period. Maximum gentamicin concentrations in serum (10.06 +/- 2.85 micrograms/ml) occurred at 0.25 hours after injection. Maximum gentamicin concentrations in the large colon (4.13 +/- 1.80 micrograms/ml) and jejunum (2.26 +/- 1.35 micrograms/ml) occurred in horses at 0.5 and 0.33 hours, respectively. Tissue concentrations decreased in parallel with serum concentrations and were still detectable at the end of the 4-hour period. During the time that samples were collected, the total amount of gentamicin excreted in the urine ranged from 7.21 +/- 3.11 mg to 11.91 +/- 7.12 mg, with a mean urinary concentration of 57.01 +/- 5.37 micrograms/ml. Over the 4-hour collection period, the fraction of dose that was excreted unchanged in the urine was 4.8 +/- 1.9%. Pharmacokinetic analyses of the serum concentration-time data gave a serum half-life of 2.52 +/- 1.29 hours, volume of distribution of 227 +/- 83 ml/kg, and body clearance of 1.12 +/- 0.26 ml/min/kg. The half-lives of the antibiotic in the jejunum and large colon were 1.32 and 1.33 hours, respectively.     

Pharmacokinetics of sodium cephapirin in lactating dairy cows

Sodium cephapirin was administered (10 mg/kg of body weight, IM) at 8-hour intervals in 4 consecutive doses to each of 6 lactating dairy cows. Blood, normal milk, mastitic milk, urine, and endometrial tissue samples were collected serially. Mean peak cephapirin concentrations in serum were 13.3 micrograms/ml 10 minutes after the 1st injection and were 15.8 micrograms/ml 20 minutes after the 4th injection (post[initial]injection hour [PIH] 24.33). The overall elimination rate constant value was 0.66/h and plasma clearance was 760 ml/h/kg. Mean peak cephapirin concentration in normal milk was 0.11 microgram/ml at PIH 2 and mean peak cephapirin concentration in mastitic milk was 0.18 microgram/ml at PIH 4. Cephapirin was not detected in the endometrium. The highest concentration of cephapirin in urine was 452 micrograms/ml, 2 hours after the 4th dose (PIH 26).     

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.     

Pharmacokinetics of rifampin given as a single oral dose in foals

Six foals from 6 to 8 weeks of age were given a single oral dose of rifampin at a dosage of 10 mg/kg of body weight. Serum rifampin concentrations were measured serially during a 24-hour period. The mean peak serum rifampin concentration was 6.7 micrograms/ml at 4 hours after treatment. The concentration decreased slowly, and at 24 hours the mean value was 2.7 micrograms/ml. The elimination half-life was 17.5 hours, and the elimination rate constant was 0.04/hr.     

Serum and synovial fluid concentrations of ampicillin trihydrate in calves with suppurative arthritis

Eight calves with suppurative arthritis were each given a single intramuscular injection of ampicillin trihydrate at a dose of 10 mg/kg. Ampicillin concentrations were measured serially in serum and in suppurative and normal synovial fluid over a 24-hour period. The mean peak serum concentration was 2.5 +/- 0.54 micrograms/ml 2 hours after injection. The highest concentration in normal synovial fluid was 3.5 +/- 0.40 micrograms/ml at 4 hours and the highest concentration in suppurative synovial fluid was 2.7 +/- 0.58 micrograms/ml at 2 hours. Overall mean ampicillin concentration in normal synovial fluid for the first 8 h (2.9 +/- 0.32 micrograms/ml) was significantly different from that in suppurative synovial fluid (2.1 +/- 0.33 micrograms/ml) and serum (1.9 +/- 0.30 micrograms/ml; p less than 0.05).     

Pharmacokinetic and pathological evaluation of gentamicin in cats given a small intravenous dose repeatedly for five days.

Gentamicin was administered to six cats at a dosage of 3 mg/kg of body weight intravenously every 8 h for five days. Peak and trough serum gentamicin concentrations were measured after each injection. Gentamicin elimination rate and serum half-life were calculated. Serum urea nitrogen, creatinine, biochemistry profile, electrolyte, glucose, total protein, and albumin concentrations were measured daily. Urinalyses were performed before and after the five-day experimental period. The mean +/- SD peak serum gentamicin concentration was 7.19 +/- 1.10 micrograms/mL, and the trough concentration was 0.59 +/- 0.09 microgram/mL. These concentrations are known to be effective against most gentamicin-sensitive bacteria. The mean +/- SD gentamicin elimination rate was 0.0065 +/- 0.0004 min-1. The harmonic mean +/- pseudo standard deviation serum half-life of gentamicin was 107.21 +/- 12.79 min. There were no significant increases (P greater than 0.05) in clinicopathological variables. Microscopic examination of renal sections did not disclose pathological lesions. Signs of vestibular impairment were not observed. A dosage of 3 mg gentamicin/kg given intravenously every 8 h for five days was determined to be safe and to produce therapeutic blood levels in cats.     

Chloramphenicol sodium succinate in the horse: serum, synovial, peritoneal, and urine concentrations after single-dose intravenous administration

Six healthy adult mares were given a single IV dose (25 mg/kg of body weight) of chloramphenicol sodium succinate. Chloramphenicol concentrations in serum, synovial fluid, peritoneal fluid, and urine were measured serially over a 48-hour period. The highest measured serum chloramphenicol concentration was 6.21 micrograms/ml at 0.5 hour. Chloramphenicol was detected in synovial and peritoneal fluids, with mean peak concentrations of 3.89 micrograms/ml and 3.50 micrograms/ml, respectively, at 0.5 hour. Serum and synovial concentrations declined rapidly and were not measurable at 3 hours. Chloramphenicol could not be detected in peritoneal fluid at 6 hours. The serum half-life was 0.43 hour and the apparent volume of distribution was 2.83 L/kg. Urine concentrations of chloramphenicol peaked at 0.5 hour at 106.72 micrograms/ml and also declined rapidly. The drug could not be detected in the urine at 36 hours.     

Pharmacokinetics of amikacin in pony foals after a single intramuscular injection

Six healthy pony foals, from 2 to 11 days of age, were given a single IM injection of amikacin sulfate (250 mg/ml) at a dosage rate of 7 mg/kg of body weight. Serum amikacin concentrations were measured serially over a 24-hour period. The mean peak serum concentration was 14.7 micrograms/ml at 0.5 hour. The elimination rate constant for amikacin was 0.24/hour, the elimination half-life was 3.0 hours, and the apparent volume of distribution was 0.58 L/kg.     

Gentamicin sulfate in the horse: serum, synovial, peritoneal, and urine concentrations after single dose intramuscular administration

Ten healthy adult mares were given a single intramuscular dose (2.2 mg/kg) of gentamicin sulfate. Over a 48-h period, gentamicin concentrations were measured serially in the serum of all ten mares and in synovial fluid, peritoneal fluid, and urine of six of the mares. The mean peak serum gentamicin concentration was 5.73 μg/ml at 1 h. Gentamicin was detected in synovial fluid and peritoneal fluid, with mean peak gentamicin concentrations of 2.41 μg/ml and 3.92 μg/ml, respectively, observed at 2 h. These concentrations declined in parallel with serum concentrations and were not measurable at 48 h. Urine gentamicin concentration was relatively high, with a mean peak concentration of 424.9 μg/ml at 1 h after drug administration.     

Trimethoprim-sulfadiazine in the horse: serum, synovial, peritoneal, and urine concentrations after single-dose intravenous administration

Six healthy adult mares were given a single IV injection of trimethoprim (TMP)-sulfadiazine (SDZ) at a dosage rate of 2.5 mg of TMP/kg of body weight and 12.5 mg of SDZ/kg. Serum, synovial, peritoneal, and urine TMP-SDZ concentrations were measured serially over a 48-hour period. The highest measured mean concentrations of TMP and SDZ were found in the first (0.5 hour) sample of serum, synovial fluid, and peritoneal fluid. The mean peak concentrations of TMP and SDZ averaged 4.37 micrograms/ml and 21.81 micrograms/ml for serum, 2.95 micrograms/ml and 15.31 micrograms/ml for synovial fluid, and 3.88 micrograms/ml and 19.52 micrograms/ml for peritoneal fluid, respectively. Urine concentrations of the drugs were relatively high and peaked early. The elimination rate for TMP and SDZ averaged 0.41 and 0.26 hour-1, while the elimination half-life was 1.91 and 2.71 hours, respectively, and the volume of distribution averaged 0.59 and 0.52 L/kg, respectively.     

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 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.     

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 and body fluid and endometrial concentrations of cephapirin in mares

Six healthy adult horse mares were each given a single injection of sodium cephapirin (20 mg/kg of body weight, IV), and serum cephapirin concentrations were measured serially over a 6-hour period. The mean elimination rate constant was 0.78 hour-1 and the elimination half-life was 0.92 hours. The apparent volume of distribution (at steady state) and the clearance of the drug were estimated at 0.17 L/kg and 598 ml/hour/kg, respectively. Each mare was then given 4 consecutive IM injections of sodium cephapirin (400 mg/ml) at a dosage level of 20 mg/kg. Cephapirin concentrations in serum, synovial fluid, peritoneal fluid, CSF, urine, and endometrium were measured serially. After IM administration, the highest mean serum concentration was 14.8 micrograms/ml 25 minutes after the 4th injection. The highest mean synovial and peritoneal concentrations were 4.6 micrograms/ml and 5.0 micrograms/ml, respectively, 2 hours after the 4th injection. The highest mean endometrial concentration was 2.2 micrograms/g 4 hours after the 4th injection. Mean urine concentrations reached 7,421 micrograms/ml. Cephapirin did not readily penetrate the CSF. When cephapirin was given IM at the same dose, but in a less concentrated solution (250 mg/ml), serum concentrations peaked at 25.0 micrograms/ml 20 minutes after injection, but the area under the serum concentration-time curve was not significantly different (P greater than 0.05). The bioavailability of the drug was greater than or equal to 95% after IM injection.     

Pharmacokinetics of cefotaxime in the domestic cat

Cefotaxime was administered as single IV or IM dose for the purpose of examining its pharmacokinetics in healthy cats. The mean predicted plasma concentration of cefotaxime in 6 cats at 0 time after a single IV dosage of 10 mg/kg of body weight was 88.9 micrograms/ml. The mean plasma concentrations decreased to 10.8 micrograms/ml at 2 hours, 3.7 micrograms/ml at 3 hours, and 0.5 microgram/ml at 6 hours. The half-life was 0.98 +/- 0.25 hour (mean +/- SD), and the total body clearance was determined to be 2.76 +/- 1.25 ml/min/kg. After a single IM injection of 10 mg/kg of body weight, the mean maximum observed plasma concentration was 36.2 micrograms/ml at 0.75 hour. The mean absorption half-life was 0.24 hour. In 2 animals, the bioavailability of an IM injection was 98.2% and 93.0%.     

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.