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 and serum concentrations of cephapirin in neonatal foals

Six healthy foals, from 4 to 6 days of age, were given a single IM injection of sodium cephapirin (250 mg/ml) at a rate of 20 mg/kg of body weight. Serum concentrations of cephapirin were measured serially over an 8-hour period. The mean peak serum concentration was 21.2 micrograms/ml at 10 minutes. The overall elimination rate constant was 1.06/hr and the elimination half-life was 0.70 hour. The apparent volume of distribution at steady state was 1.06 L/kg and plasma clearance was 1,105 ml/hr/kg.     

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.     

Amikacin sulfate in mares: pharmacokinetics and body fluid and endometrial concentrations after repeated intramuscular administration

Six mares were given 5 IM injections (at 12-hour intervals between doses) of amikacin sulfate at a dosage of 7 mg/kg of body weight. Serum amikacin concentrations were measured serially throughout the study; synovial, peritoneal, endometrial, and urine concentrations were determined after the last injection. Amikacin concentrations of the CSF were measured serially in 3 of the 6 mares; 1 of the 3 mares had septic meningitis. Mean serum amikacin concentrations peaked at 1 to 2 hours after IM injection. The highest mean serum concentration was 19.2 micrograms/ml (1.5 hours after the 5th injection). The highest mean synovial concentration was 10.8 micrograms/ml at 2 hours after the 5th injection; the highest mean peritoneal concentration was 16.2 micrograms/ml at 3 hours after the 5th injection. The mean endometrial amikacin concentration was 2.5 micrograms/g (1.5 hours after the 5th injection). Amikacin reached a CSF concentration of 0.97 micrograms/ml in the mare with meningitis, but amikacin was not detected in CSF of healthy mares. Urine concentrations reached 1,458 micrograms/ml. Pharmacokinetic values were estimated after the 1st injection (elimination rate constant = 0.31/hour; half-life = 2.3 hours; apparent volume of distribution = 0.26 L/kg), and after the 5th injection (elimination rate constant = 0.28/hour; half-life = 2.6 hours; apparent volume of distribution = 0.30 L/kg); significant differences were not observed.     

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 sodium amoxicillin in foals after intramuscular administration

Pharmacokinetic values of sodium amoxicillin (22 mg/kg of body weight) in foals were determined after a single IM injection in 6 Quarter Horse foals at 3, 10, and 30 days of age. Serum amoxicillin concentrations were measured serially over a 24-hour period. The absorption of amoxicillin was rapid and followed a 1st-order elimination. Mean peak serum concentrations occurred 30 minutes after the injection in foals at all ages and were 17.31 +/- 9.59 micrograms/ml when the foals were 3 days old, 23.28 +/- 9.86 micrograms/ml when the foals were 10 days old, and 21.35 +/- 6.39 micrograms/ml when the foals were 30 days old. Serum samples collected beyond 8 hours after administration contained amoxicillin concentrations less than 0.05 micrograms/ml. The elimination rate constant increased with increasing age (0.5265 +/- 0.0891 hour-1 when the foals were 3 days old, 0.6494 +/- 0.1114 hour-1 when the foals were 10 days old, and 0.7112 +/- 0.1016 hour-1 when the foals were 30 days old). Serum clearance increased with increasing age (498.4 +/- 82.6 ml/hr/kg at 3 days, 631.6 +/- 170.5 ml/hr/kg at 10 days, and 691.2 +/- 127.3 ml/hr/kg at 30 days). Serum half-life decreased with increasing age (1.34 +/-0.243 hour at 3 days, 1.10 +/- 0.239 hour at 10 days, and 0.991 +/- 0.139 hour at 30 days), whereas the extrapolated concentration at time zero and apparent volume of distribution did not change during the first 30 days of age.     

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.     

Pharmacokinetics of flunixin meglumine in dogs

The pharmacokinetics of flunixin meglumine, a potent nonsteroidal anti-inflammatory agent, were studied in 6 intact, awake dogs. Plasma samples were obtained up to 12 hours after IV administration of flunixin meglumine. Flunixin concentration was determined, using high performance liquid chromatography. Plasma data best fit a 2-compartment model. Distribution half-life was 0.55 hour; elimination half-life was 3.7 hours; volume of distribution (area) was 0.35 L/kg; volume of distribution at steady state was 0.18 L/kg; volume of the central compartment was 0.079 L/kg; and total body clearance was 0.064 L/hr/kg. Flunixin concentrations obtained over a 6-hour period in 3 dogs with septic peritonitis did not differ significantly from those obtained from healthy dogs.     

Pharmacokinetics and body fluid and endometrial concentrations of trimethoprim-sulfamethoxazole in mares

Six healthy adult mares were each given a single IV injection of trimethoprim (TMP)-sulfamethoxazole (SMZ) at a dosage of 2.5 mg of TMP/kg of body weight and 12.5 mg of SMZ/kg. Serum concentrations of each drug were measured serially over a 24-hour period. For TMP, the mean overall elimination rate constant (K) was 0.43/hr and the elimination half-life (t1/2) was 1.9 hours. The apparent volume of distribution (at steady state) was 1.62 L/kg and TMP clearance was 886 ml/hr/kg. For SMZ, K was 0.22/hr and t1/2 was 3.53 hours. The apparent volume of distribution at steady state was 0.33 L/kg and SMZ clearance was 78.2 ml/hr/kg. Each mare was then given 5 consecutive oral doses of TMP-SMZ at a rate of 2.5 mg of TMP/kg and 12.5 mg of SMZ/kg at 12-hour intervals. Trimethoprim and SMZ concentrations were measured in serum, synovial fluid, peritoneal fluid, CSF, urine, and endometrium. Although both mean TMP and SMZ serum concentrations were higher after the 5th dose than after the 1st dose, only the mean TMP concentration was significantly (P less than 0.05) different. After the 5th oral dose, concentrations of TMP and SMZ attained in body fluids (except CSF) and endometrial tissue were equal to or exceeded reported minimum inhibitory concentrations for Corynebacterium pseudotuberculosis, Staphylococcus sp, Streptococcus zooepidemicus, and several obligate anaerobes. Absorption of both drugs was variable after oral administration.     

Clinical pharmacokinetics of amikacin in dogs

After IV, IM, and subcutaneous injection of single dosages of amikacin (5, 10, and 20 mg/kg of body weight) in each of 4 dogs, the elimination kinetics of amikacin were determined. The pattern of urinary excretion and cumulative amount excreted unchanged in 24 hours were also determined. Amikacin had a short half-life (approx 1 hour) that was independent of the dosage. Intravenous injection of 10 mg/kg gave apparent volume of distribution of 226 +/- 37 ml/kg and body clearance of 2.64 +/- 0.24 ml/min.kg (mean +/- SD, n = 4). Within 6 hours, greater than 90% of the antibiotic was excreted in the urine, regardless of the route of administration. For isolates of common bacterial species from the canine urinary tract, minimum inhibitory concentrations of amikacin, gentamicin, tobramycin, and kanamycin were determined in vitro. Cumulative percentages were approximately the same for urinary isolates of Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, and coagulase-positive staphylococci that were susceptible (minimum inhibitory concentrations less than or equal to 32 micrograms/ml) to increasing concentrations of amikacin, gentamicin, and tobramycin, in vitro. Klebsiella pneumoniae was significantly more susceptible to amikacin than were the other bacteria evaluated. Widest variations in susceptibility to aminoglycosides were found with urinary isolates of streptococcal species. For dogs with normal renal function, an amikacin dosage of 10 mg/kg (IM or subcutaneously) is recommended every 8 hours for treatment of systemic infections, and every 12 hours for treatment of urinary tract infections caused by susceptible bacteria.     

Combined pharmacokinetics of gentamicin in pony mares after a single intravenous and intramuscular administration

Healthy mature pony mares (n = 6) were given a single dose of gentamicin (5 mg/kg of body weight) IV or IM 8 days apart. Venous blood samples were collected at 0, 5, 10, 20, 30, and 45 minutes and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, 30, 36, 40, and 48 hours after IV injection of gentamicin, and at 10, 20, 30, and 45 minutes and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, and 30 hours after IM injection of gentamicin. Gentamicin serum concentration was determined by a liquid-phase radioimmunoassay. The combined data of IV and IM treatments were analyzed by a nonlinear least-square regression analysis program. The kinetic data were best fitted by a 2-compartment open model, as indicated by residual trends and improvements in the correlation of determination. The distribution phase half-life was 0.12 +/- 0.02 hour and postdistribution phase half-life was 1.82 +/- 0.22 hour. The volume of the central compartment was 115.8 +/- 6.0 ml/kg, volume of distribution at steady state was 188 +/- 9.9 ml/kg, and the total body clearance was 1.27 +/- 0.18 ml/min/kg. Intramuscular absorption was rapid with a half-life for absorption of 0.64 +/- 0.14 hour. The extent of absorption was 0.87 +/- 0.14. Kinetic calculations predicted that IM injections of 5 mg of gentamicin/kg every 8 hours would provide average steady-state serum concentrations of 7.0 micrograms/ml, with maximum and minimum steady-state concentrations of 16.8 and 1.1 micrograms/ml, respectively.     

Pharmacokinetics of procainamide hydrochloride in dogs

Pharmacokinetics of procainamide hydrochloride were studied in 2 groups of dogs. In a group of 6 dogs, procainamide was administered IV at a small dose of 8 mg/kg (group 1), and blood samples were obtained for 3.5 hours. In another group of 6 dogs, procainamide was administered IV and orally at an average dose of 25.5 mg/kg (group 2) in a crossover manner. Blood samples were obtained for 48 hours. In 2 dogs (previously used in part II), N-acetylprocainamide (NAPA) was administered IV at a dose of 10 mg/kg. Plasma samples were assayed for procainamide by fluorescence polarization immunoassay, and NAPA samples were assayed by high-performance liquid chromatography. In group 1, the elimination of procainamide was described by a 1-compartment, open pharmacokinetic model. The elimination half-life was 2.43 hours, the apparent volume of distribution was 1.44 L/kg, and the systemic clearance was 0.412 L/kg/hr. In group 2, 2 of the 6 dogs were described by a 1-compartment model, and 4 of the 6 dogs were described with a 2-compartment pharmacokinetic model. The elimination half-life for the IV dosage was 2.85 hours, the apparent volume of distribution was 2.13 L/kg, and the systemic clearance was 0.519 L/kg/hr. For the orally administered dose, the bioavailability was 85%, and the absorption half-life was 0.5 hours. There was no evidence of acetylation of procainamide to NAPA or deacetylation of NAPA to procainamide. The estimated elimination half-life of NAPA was 4.7 hours.     

Pharmacokinetics of intravenously and intramuscularly administered ticarcillin and clavulanic acid in foals

Serum concentrations of ticarcillin and clavulanic acid were measured in healthy foals (2 to 6 months old) given the drugs in combination by intravenous and intramuscular routes of administration. Five foals were administered 50 mg of ticarcillin/kg of body weight and 1.67 mg of clavulanic acid/kg, IV. Five foals were administered 100 mg of ticarcillin/kg and 3.33 mg of clavulanic acid/kg, IV, and 4 of those 5 were given the same combined dose IM. The elimination half-life of ticarcillin for intravenous administration was 0.83 hour for the low dosage and 0.96 hour for the high dosage. After intramuscular administration, the half-life of elimination was 2.9 hours, with bioavailability of 54.6%. For IV administered clavulanic acid, the elimination half-life was 0.65 hour for the low dosage and 0.74 hour for the high dosage. After intramuscular administration, the elimination half-life was 0.92 hour, and bioavailability was 68.1%. A combined dosage, 50 mg of ticarcillin/kg and 1.67 mg of clavulanic acid/kg, given every 6 hours is recommended.     

Pharmacokinetic disposition of theophylline in horses after intravenous administration

The pharmacokinetics of theophylline were determined in 6 healthy horses after a single IV administration of 12 mg of aminophylline/kg of body weight (equivalent to 9.44 mg of theophylline/kg). Serum theophylline was measured after the IV dose at 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 15 hours. Serum concentration plotted against time on semilogarithmic coordinates, indicated that theophylline in 5 horses was best described by a 2-compartment open model and in 1 horse by a 1-compartment open model. The following mean pharmacokinetic values were determined; elimination half-life = 11.9 hours, distribution half-life = 0.495 hours, apparent specific volume of distribution = 0.885 +/- 0.075 L/kg, apparent specific volume of central compartment = 0.080 L/kg, and clearance = 51.7 +/- 11.2 ml/kg/hr. Three horses with reversible chronic obstructive pulmonary disease were serially given 1, 3, 6, 9, 12, and 15 mg of aminophylline/kg in single IV doses (equivalent to 0.8, 2.4, 4.7, 7.1, 9.44, and 11.8 mg of theophylline/kg, respectively). The horses were exposed to a dusty barn until they developed clinical signs of respiratory distress and were then given the aminophylline. Effects of increasing doses on different days were correlated with clinical signs, blood pH, and blood gases. The 3 horses had a decrease in the severity of clinical signs after the 9, 12, or 15 mg doses of aminophylline/kg. The horses at 0.5 hour after dosing had a significant decrease in PaCO2 (43.6 +/- 5.5 to 39.4 +/- 6.7 mm of Hg, P less than 0.001) and a significant increase in blood pH (7.38 +/- 0.017 to 7.41 +/- 0.023, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of ceftazidime in dogs following subcutaneous administration and continuous infusion and the association with in vitro susceptibility of Pseudomonas aeruginosa

OBJECTIVE: To determine the pharmacokinetics of ceftazidime following subcutaneous administration and continuous IV infusion to healthy dogs and to determine the minimum inhibitory concentration (MIC) of ceftazidime for clinical isolates of Pseudomonas aeruginosa. ANIMALS: 10 healthy adult dogs. PROCEDURE: MIC of ceftazidime for 101 clinical isolates of P aeruginosa was determined in vitro. Serum concentrations of ceftazidime were determined following subcutaneous administration of ceftazidime (30 mg/kg of body weight) to 5 dogs and continuous IV infusion of ceftazidime (loading dose, 4.4 mg/kg; infusion rate, 4.1 mg/kg/h) for 36 hours to 5 dogs. RESULTS: The MIC of ceftazidime for P aeruginosa was < or = 8 microg/ml; all isolates were considered susceptible. Following SC administration of ceftazidime, mean beta disappearance half-life was 0.8 hours, and mean serum ceftazidime concentration exceeded the MIC for P aeruginosa for only 4.3 hours. Two dogs had gastrointestinal tract effects. Mean serum ceftazidime concentration exceeded 16 microg/ml during continuous IV infusion. None of the dogs developed adverse effects. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of ceftazidime subcutaneously (30 mg/kg, q 4 h) or as a constant IV infusion (loading dose, 4.4 mg/kg; rate, 4.1 mg/kg/h) would maintain serum ceftazidime concentrations above the MIC determined for 101 clinical isolates of P aeruginosa. Use of these dosages may be appropriate for treatment of dogs with infections caused by P 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)     

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.     

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%.     

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 bioavailability of cephalothin in horse mares

The pharmacokinetics and bioavailability of cephalothin given to 6 horse mares at a dosage level of 11 mg/kg of body weight IV or IM were investigated. The disposition of cephalothin given IV was characterized by a rapid disposition phase with a mean half-life of 2.89 minutes and a subsequent slower elimination phase with a mean half-life of only 14.7 minutes. The mean residence time of cephalothin was 10.6 +/- 2.11 minutes. The total plasma clearance of cephalothin averaged 13.6 ml/min/kg and was caused by metabolism and renal elimination. Renal clearance of cephalothin averaged 1.32 ml/min/kg and accounted for elimination of about 10.1% of the administered dose. The volume of distribution at steady state averaged 151 mg/kg. Plasma protein binding of cephalothin at a concentration of 10 micrograms/ml averaged 17.9 +/- 2.5%. Cephalothin was rapidly metabolized to desacetylcephalothin. Maximum plasma desacetylcephalothin concentrations were observed in the blood samples collected 5 minutes after IV doses and averaged 22.9 micrograms/ml. The apparent half-life of desacetylcephalothin in plasma was 41.6 minutes and its renal clearance averaged 4.49 +/- 2.43 ml/min/kg. An average of 33.9% of the dose was recovered in the urine as desacetylcephalothin. The maximum plasma cephalothin concentration after IM administration was 11.3 +/- 3.71 micrograms/ml. The terminal half-life was 47.0 minutes and was longer than the half-life after IV administration. The bioavailability of cephalothin given IM ranged from 38.3% to 93.1% and averaged 65.0 +/- 20.5%.