Effect of premedication with acetylpromazine on the disposition kinetics of thiopental

This study was performed to determine whether premedication with acetylpromazine alters the disposition kinetics of thiopental in normal dogs. Based on nonlinear least squares regression analysis of the plasma concentration-time data obtained in individual dogs, a three-compartment open model was selected to describe the pharmacokinetic behavior of thiopental. While clinically premedication appears to delay time of awakening from thiopental anesthesia, statistical comparison (Student's t-test for paired data) of pharmacokinetic terms showed no significant difference. This may be largely attributed to wide individual variation in each parameter. The rate of change in volume of distribution at zero time (mean +/- SD, n = 7), which is a parameter that might have been expected to vary significantly, was 97 +/- 106 ml/min X kg for thiopental alone and 77 +/- 60 ml/min X kg following acetylpromazine premedication. Body clearance of thiopental was 1.96 +/- 0.59 ml/min X kg in dogs without premedication and 1.55 +/- 0.49 ml/min X kg following acetylpromazine. By relating observed time of awakening to plasma concentrations of thiopental it was determined that awakening from anesthesia occurred at a concentration of 20 micrograms/ml whether or not the dogs were premedicated. It can only be concluded that while premedication with acetylpromazine appears to delay time of awakening from anesthesia, it does not change the disposition kinetics of thiopental or affect the plasma concentration at the observed time of awakening.     

Cefadroxil in the horse: pharmacokinetics and in vitro antibacterial activity

Sodium cefadroxil was administered as a single intravenous dose (25 mg/kg) to six healthy adult mares. Plasma samples were collected over a 24-h period and cefadroxil concentrations were measured by microbiological assay. The pharmacokinetic behavior of the drug was appropriately described in terms of a one-compartment open model. Values for the major pharmacokinetic terms were: extrapolated initial plasma concentration = 59.2 +/- 15.0 micrograms/ml; half-life = 46 +/- 20 min; apparent volume of distribution = 462 +/- 191 ml/kg; and body clearance = 7.0 +/- 0.6 ml/min.kg. In a subsequent study, a suspension of cefadroxil monohydrate was administered intragastrically (25 mg/kg) to the same six horses. Plasma concentrations of the drug peaked at 1-2 h but, in general, absorption was both poor and inconsistent. The data were unsuitable for determination of cefadroxil bioavailability from this oral dosage form. Ninety-nine isolates of eleven bacterial species obtained from clinically ill horses were tested for susceptibility to cefadroxil. All strains of Streptococcus equi, Streptococcus zooepidemicus, coagulase-positive staphylococci, Corynebacterium pseudotuberculosis and five out of six strains of Actinobacillus suis were highly susceptible to the drug (MIC less than 4 micrograms/ml). Escherichia coli, Klebsiella pneumoniae and Salmonella sp. showed intermediate susceptibility (MIC 4-16 micrograms/ml), while all isolates of Corynebacterium (Rhodococcus) equi, Enterobacter cloacae and Pseudomonas aeruginosa proved to be highly resistant to cefadroxil (MIC greater than 128 micrograms/ml).     

Comparative study of the pharmacokinetics of alfentanil in rabbits, sheep, and dogs

The central arterial pharmacokinetics of alfentanil, a short-acting opioid agonist, were studied in rabbits, sheep, and dogs after short-duration infusion of the drug. Alfentanil was infused until a set end point (high-amplitude, slow-wave activity on the EEG) was reached. This required a larger alfentanil dose and a higher alfentanil arterial concentration in sheep, compared with rabbits and dogs. The plasma concentration-time data for each animal were fitted, using nonlinear regression, and in all animals, were best described by use of a triexponential function. In this study, differences in the disposition kinetics of alfentanil among the 3 species were found for only distribution clearance and initial distribution half-life. In dogs, compared with rabbits and sheep, the first distribution half-life was longer, probably because of pronounced drug-induced bradycardia (mean +/- SD, 48 +/- 21 beats/min). Distribution clearance was faster in sheep, compared with dogs, also probably because of better blood flow in sheep. Elimination half-life was similar in all species (rabbits, 62.4 +/- 11.3 minutes; sheep, 65.1 +/- 27.1 minutes; dogs, 58.3 +/- 10.3 minutes). This rapid half-life resulted from a small steady-state volume of distribution (rabbits, 908.3 +/- 269.0 ml/kg; sheep, 720.0 +/- 306.7 ml/kg; dogs, 597.7 +/- 290.2 ml/kg) and rapid systemic clearance (rabbits, 19.4 +/- 5.3 ml/min/kg; sheep, 13.3 +/- 3.0 ml/min/kg; dogs, 18.7 +/- 7.5 ml/min/kg). On the basis of these pharmacokinetic variables, alfentanil should have short duration of action in rabbits, sheep, and dogs. This may be beneficial in veterinary practice where rapid recovery would be expected after bolus administration for short procedures or after infusion for longer procedures.     

Probenecid effect on cefuroxime pharmacokinetics in calves

Cefuroxime pharmacokinetics were studied in unweaned calves. The antibiotic was administered at 10 mg/kg to six calves i.v., to 12 calves i.m. and to ten of the previous 12 calves i.m. at 10 mg/kg together with probenecid at 40 mg/kg. Intramuscular doses of cefuroxime alone at 20 mg/kg were given to seven calves; to five of these calves cefuroxime was also given together with probenecid at 40 mg/kg and at 80 mg/kg. The serum concentration-time data were analyzed using statistical moment theory (SMT). The elimination half-life (t1/2) was 69.2 min (harmonic mean) after i.v. and 64.8 min and 64.9 min following i.m. administration of the lower and higher dose, respectively. Co-administration of probenecid did not affect the t1/2. The mean residence time (MRT) was 80.9 +/- 23.5 min (mean +/- SD) after i.v. and 117.8 +/- 9.3 min and 117.7 +/- 5.4 min after i.m. administration of cefuroxime at 10 and 20 mg/kg, respectively. The MRTi.m. following administration of cefuroxime at 10 mg/kg together with probenecid at 40 mg/kg was 140.0 +/- 8.8 min. The MRTi.m. values were 132.8 +/- 2.3 min and 150.8 +/- 5.1 min after cefuroxime was given at 20 mg/kg together with probenecid at 40 mg/kg or 80 mg/kg, respectively. The total body clearance (ClT) was 3.56 +/- 1.11 ml/min/kg and the volume of distribution at steady state (Vd(ss] 0.270 +/- 0.051 l/kg. The MIC90 values of cefuroxime were 16 micrograms/ml for E. coli and Salmonella isolates, 0.5 microgram/ml for Pasteurella multocida and 2.0 micrograms/ml for P. haemolytica.     

Pharmacokinetics and renal clearance of ampicillin in sheep

Pharmacokinetics and renal clearance of ampicillin were investigated in 13 sheep, following one single oral dose of 750 mg. A peak concentration in plasma 0.38 +/- 0.04 microgram/ml (mean +/- SEM) was achieved 95.3 +/- 5.95 min after drug administration. Absorption half-life was 44.4 +/- 4.4 min. The area under the plasma concentration curve was 94.6 +/- 4.5 micrograms.hour.ml-1, while in the case of urine it was 370.5 +/- 28.3 micrograms.hour.ml-1. Biological half-life of ampicillin was 110 +/- 3 min, with an elimination rate constant of 0.0064 +/- 0.0002 min-1. The values for volume of distribution and total body clearance were 8.2 +/- 0.71/kg or 52.0 +/- 4.2 ml/kg/min, respectively. The priming and maintenance doses, using MIC as 0.05 microgram/ml, were suggested to be 8.8 or 8.4 mg/kg, respectively, at an 8-h interval. For MIC of 0.5 microgram/ml, this dose should be 10 times higher. Renal clearance of ampicillin seemed to involve active tubular secretion. Renal excretion indicated either extensive metabolism or excretion through routes other than kidneys.     

Potency of rapidly acting barbiturates in dogs, using inhibition of the laryngeal reflex as the end point

Thiopental, thiamylal, and methohexital were administered to 30 dogs to determine equipotent doses necessary to inhibit laryngeal reflexes. The doses studied were 7.1, 10.0, 14.1, 20.0, and 28.3 mg of thiopental/kg of body weight; 5.7, 8.0, 11.3, 16.0, and 22.6 mg of thiamylal/kg; and 3.5, 5.0, 7.1, 10.0, and 14.1 mg of methohexital/kg. At 1, 2.5, 5, and 10 minutes after injection, the presence or absence of the laryngoscopic reflex, pedal reflex, and jaw tone were recorded. The times for return of each reflex, as well as the ability to walk 10 steps without assistance, were also recorded. Using the method of least squares, a probit analysis was performed on the quantal responses at 1 minute. The effective dose in 50% of the population for the laryngoscopic reflex was chosen as the end point for intubation, and the computed doses necessary to achieve this end point were 19.4 mg of thiopental/kg, 18.4 mg of thiamylal/kg, and 9.7 mg of methohexital/kg. When potencies of the drugs were compared with that of thiopental (1), thiamylal was found to be equipotent (1.06) and methohexital twice as potent (2.0). At the accepted clinical dose, recovery times for thiopental (71.1 +/- 7.2 minutes) and thiamylal (75.3 +/- 7.7 minutes) were similar, and twice that for methohexital (33.9 +/- 4.6 minutes).     

The effects of halothane and nitrous oxide on the pharmacokinetics of propofol in dogs

The pharmacokinetics of propofol, 6.5 mg/kg, administered as a bolus dose intravenously (i.v.) were studied in six dogs (group 1). The effect of maintaining anaesthesia with halothane and nitrous oxide in oxygen on propofol pharmacokinetics was also investigated in six dogs undergoing routine anaesthesia (group 2). Induction of anaesthesia was rapid in all animals. Post-induction apnoea was a feature in three of the 12 dogs. The blood propofol concentration-time profile was best described by a bi-exponential decline in two dogs in group 1 and in 3 dogs in group 2, and by a tri-exponential decline in four dogs in group 1 and 3 dogs in group 2. The elimination half-life was long in both groups (90.9 min and 75.2 min, respectively), the volume of distribution at steady state large (4889 and 4863 ml/kg) and the clearance rapid (58.6 and 56.3 ml/kg.min). There were no significant differences between the groups, thus indicating that maintenance of anaesthesia with halothane and nitrous oxide had no effect on the pharmacokinetics of propofol in the dog.     

Evaluation of the arrhythmogenicity of a low dose of acepromazine: comparison with xylazine.

Alteration in the arrhythmogenic dose of epinephrine (ADE) was determined in 6 healthy dogs under halothane anesthesia following the administration of xylazine at 1.1 mg/kg i.v. and acepromazine at 0.025 mg/kg i.v. The order of treatment was randomly assigned with each dog receiving both treatments and testing was carried out on 2 separate occasions with at least a 1 wk interval. The ADE determinations were made prior to drug administration during halothane anesthesia (CNTL) and then 20 min and 4 h following drug treatment. Epinephrine was infused for 3 min at increasing dose rates (2.5, 5.0, 10.0 micrograms/kg/min) until the arrhythmia criterion (4 or more intermittent or continuous premature ventricular contractions) was reached within the 3 min of infusion or the 1 min following cessation. The interinfusion interval was 20 min. There was a significant difference (P = 0.0001) in the ADE determined following acepromazine administration at 20 min (20.95 micrograms/kg +/- 2.28 SEM) compared to CNTL (6.64 micrograms/kg +/- 1.09), xylazine at 20 min (5.82 micrograms/kg +/- 0.95) and 4 h (6.13 micrograms/kg +/- 1.05), and acepromazine at 4 h (7.32 micrograms/kg +/- 0.34). No other significant differences existed (P < 0.05). In this study we were unable to show any sensitization to epinephrine following xylazine administration during halothane anesthesia, while a protective effect was shown with a low dose of acepromazine.     

Comparison of two thiopental infusion rates for the induction of anaesthesia in dogs

OBJECTIVE: To compare the induction dose requirements of thiopental using two different infusion rates for induction of anaesthesia in dogs. STUDY DESIGN: Prospective, randomized study. ANIMALS: Fifty, healthy (ASA I or II) client-owned dogs with a mean age of 4.1 years and a mean mass of 20.4 kg undergoing elective surgery. MATERIALS AND METHODS: Animals were randomly assigned to receive an infusion of 2.5% thiopental at a rate of either 0.1 ml kg(-1) minute(-1) or 0.4 ml kg(-1)minute(-1), 30-40 minutes after pre-anaesthetic medication with intramuscular acepromazine (0.025 mg kg(-1)) and pethidine (3.5 mg kg(-1)). Thiopental administration was controlled by a precision syringe driver. Statistical analyses of the results, using the outcome 'mg kg(-1) required for induction' (log-transformed) included unpaired t-tests for all categorical data (thiopental infusion rate, breed, sex, obesity, sedation quality) and univariable linear regression for continuous variables (mass, age). All variables were then considered in a multivariable linear regression model. The quality of induction with the two different infusion rates was also assessed. RESULTS: After controlling for quality of sedation, the thiopental induction dose requirement was significantly less (p < 0.001) with the slower infusion rate (median = 7.5 mg kg(-1); range 4.9-13.7) compared with the faster infusion rate (median =11.0 mg kg(-1); range 6.6-18.0). The quality of sedation also affected the dose required (p = 0.03). The slower infusion rate was associated with a significantly poorer induction quality (p = 0.03) [corrected] CONCLUSIONS: Slow thiopental infusion (0.1 ml kg(-1) minute(-1)) for anaesthesia induction after acepromazine/pethidine pre-anaesthetic medication reduced the induction dose requirement, although the quality of induction was inferior. CLINICAL RELEVANCE: The induction dose of thiopental was reduced with a slower administration rate and so slow administration is recommended in thiopental-sensitive animals.     

Bioavailability of four slow-release theophylline formulations in the Beagle dog

Theophylline was administered to six Beagles intravenously (Aminophyllin Injectable, Searle Laboratories) and orally as four sustained-release formulations (Choledyl -SA Tablets, Parke-Davis; Theo-Dur Tablets, Key Pharmaceuticals; Theo-24 Capsules, Searle Laboratories, and Slo-bid Gyrocaps, William H. Rorer, Inc.). Values were determined for mean residence time, mean absorption time, absolute bioavailability, time to peak plasma concentration, and peak plasma concentration normalized to a theophylline dose of 20 mg/kg. In this order the values found for each formulation were: Choledyl (10.2 +/- 1.8 h, 2.8 +/- 2.2 h, 63 +/- 10%, 3.9 +/- 1.0 h, 10 +/- 1.1 micrograms/ml), Theo-Dur (12.1 +/- 5.2 h, 4.9 +/- 5.3 h, 76 +/- 18% 4.7 +/- 3.1 h, 12 +/- 3.7 micrograms/ml), Theo-24 (15.6 +/- 8.9 h, 8.1 +/- 8.4 h, 30 +/- 16%, 3.6 +/- 1.7 h, 3.5 +/- 1.3 micrograms/ml), and Slo-bid (11.9 +/- 1.9 h, 4.4 +/- 1.3 h, 60 +/- 9%, 4 +/- 1.1 h, 8.6 +/- 0.8 micrograms/ml). Choledyl, Theo-Dur and Slo-bid appear to have absorption characteristics which, if given twice daily, would maintain therapeutic plasma concentrations of theophylline between 10 and 20 micrograms/ml in the dog. Of these, Theo-Dur was predicted to provide the least peak:trough fluctuation in theophylline plasma concentrations.     

Comparative study of the cardiovascular effects of losartan in normal and in water- and salt-depleted sheep

The cardiovascular effects of losartan, a non-peptidic angiotensin II (ANG II) receptor antagonist, were studied in sheep. Eight normotensive, conscious sheep were tested twice: first under normal conditions and second when subjected to water and electrolytic depletion (furosemide 5 mg/kg twice a day for 3 days). Intravenous injection of 30 mg/kg losartan lowered the mean arterial blood pressure (MABP) in both control and water- and electrolyte-depleted sheep alike. The maximal decrease in MABP was significantly greater in diuretic-treated sheep than in controls (20.0 +/- 2.7 vs 9.3 +/- 1.1 mmHg) and occurred earlier (8.0 +/- 3.3 min vs 12.1 +/- 2.9 min). The decrease in blood pressure was associated with tachycardia in both controls and diuretic-treated sheep (+5.5 +/- 1.8 vs +11.3 +/- 3.9 beats/min). The vasopressor response to 0.1 microg/kg ANG II administered 30 min after losartan was completely antagonized. Two hours after losartan administration, MABP was on the increase in all animals and ANG II receptor blockade was partially obliterated in control sheep. The more marked cardiovascular effects recorded in diuretic-treated sheep as compared to control animals were associated with an increased activation of the renin-angiotensin system (plasma renin concentration: 6.51 +/- 1.33 vs 1.42 +/- 0.37 ng angiotensin I/ml/hr).     

Pharmacokinetics of single doses of cefoxitin given by the intravenous and intramuscular routes to unweaned calves

Cefoxitin pharmacokinetics and bioavailability were studied in unweaned calves. The antibiotic was administered to nine calves intravenously (i.v.), to seven calves intramuscularly (i.m.) at 20 mg/kg and to eight calves i.m. at 20 mg/kg together with probenecid at 40 mg/kg. Serum concentration versus time data were analysed using statistical moment theory (SMT). The i.v. data were also fitted by a linear, open two-compartment model. The elimination half-life (t1/2) was 66.9 +/- 6.9 min (mean +/- SD) after i.v. and 81.0 +/- 10.9 min after i.m. administration. The t1/2 increased to 125.5 +/- 15.6 min by the co-administration of probenecid. The total body clearance (ClT) was 4.88 +/- 1.71 ml/min/kg and the volume of distribution (Vss) 0.3187 +/- 0.0950 l/kg. The mean residence time (MRT) was 68.2 +/- 12.3 min after i.v. and 118.6 +/- 16.8 min after i.m. injection and increased to 211.5 +/- 16.8 min by the co-administration of probenecid. The mean absorption time (MAT) was 50.6 min and the estimated bioavailability (F) of cefoxitin after i.m. administration was 73.8%. The cefoxitin protein binding ranged from 55.0 to 42.0% at concentrations from 2 to 50 micrograms/ml. The MIC90 values for cefoxitin were 6.25 micrograms/ml for E. coli and Salmonella group B isolates, 3.13 micrograms/ml for Salmonella group C and D and Pasteurella multocida. There were no statistically significant differences between the pharmacokinetic parameters calculated by SMT or compartmental analysis. SMT provided an additional independent parameter, the MRT, for characterization of drug disposition kinetics.     

Pharmacokinetics of enrofloxacin after intravenous and intramuscular injection in rabbits.

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

Effects of phenobarbital on thiopental pharmacokinetics in greyhounds

The effects of phenobarbital on the pharmacokinetics of thiopental (15 mg/kg IV) were investigated in 12 trained racing Greyhounds. Phenobarbital (16 mg/kg of body weight, PO, q 24 h), administered for 14 days, reduced the area under the curve of plasma concentration of thiopental vs time from 10,688 micrograms.min/ml to 3,224 micrograms.min/ml. Furthermore, the time to recovery from anesthesia (ie, return to standing position) decreased from 103 minutes to 35.7 minutes after phenobarbital. These effects were attributed to an increase in the metabolic clearance of thiopental, as a result of induction of liver enzyme activity by phenobarbital. These results suggested that hepatic metabolism, in addition to distribution, is a factor that must be considered when assessing the difference in drug disappearance rates between Greyhounds and other breeds of dogs.     

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)     

Pharmacokinetic disposition of an immediate-release aminophylline and a sustained-release theophylline formulation in the horse

The pharmacokinetic disposition of theophylline was determined by high-performance liquid chromatographic analysis of plasma samples from six healthy, adult horses following the administration of intravenous aminophylline (dosed at 9.94 mg/kg as theophylline), immediate-release aminophylline tablets (dosed at 9.94 mg/kg as theophylline), and sustained-release theophylline tablets (dosed at 20 mg/kg). The elimination rate constant (lambda z), apparent volume of distribution (Vz), and clearance (Cl) determined by compartmental analysis of the intravenous data were 0.07 +/- 0.01 h-1, 0.80 +/- 0.06 l/kg, and 0.06 +/- 0.01 l/kg/h (mean +/- SD), respectively. Mean residence time determined by statistical moment theory of the oral data was different (P less than 0.05) for the immediate-release aminophylline (13.8 +/- 2.8 h) and sustained-release theophylline (18.2 +/- 2.3 h) formulation. Immediate-release aminophylline tablets quickly achieved peak theophylline plasma concentration of 11.51 +/- 1.4 micrograms/ml at 1.6 +/- 0.6 h while the sustained-release theophylline tablets were more slowly absorbed and achieved peak theophylline concentrations of 17.20 +/- 1.3 micrograms/ml at 7.3 +/- 1.0 h. Absolute bioavailability was 87% for the immediate-release and 97% for the sustained-release formulation. Using the principle of superposition, a loading dose of 20 mg/kg of the sustained-release formulation followed by maintenance doses of 15 mg/kg every 24 h was predicted to achieve trough-peak theophylline plasma concentrations between 6 and 17 micrograms/ml.     

Pharmacokinetics of single-dose administration of moxalactam in unweaned calves

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

Pharmacokinetics of 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 amikacin in the horse following intravenous and intramuscular administration

The pharmacokinetics of amikacin sulfate (AK) were studied in the horse after intravenous (i.v.) and intramuscular (i.m.) administration. Serum (Cs), synovial (Csf) and peritoneal (Cpf) fluid concentrations of the drug were measured. Doses of 4.4, 6.6 and 11.0 mg/kg were given. The concentrations at 15 min following i.v. injection were 30.3 +/- 0.3, 61.2 +/- 6.9 and 122.8 +/- 7.4 micrograms/ml, respectively, for the 4.4, 6.6 and 11.0 mg/kg doses. Mean peak Cs values after the intramuscular injections occurred at 1.0 h post-injection and were 13.3 +/- 1.6, 23.0 +/- 0.6 and 29.8 +/- 3.2 micrograms/ml, respectively. The t 1/2 of amikacin was 1.44, 1.57 and 1.14 h for the 4.4, 6.6 and 11.0 mg/kg doses, respectively. In this study, minimum inhibitory concentrations (MIC) of amikacin sulfate were determined for six pathogens. Based on the MIC and the pharmacokinetic parameters, it would appear that the usual therapeutic dose of amikacin would be between 4.4 and 6.6 mg/kg twice daily and, for the more serious life-threatening infections, dosing three times a day.     

Deconvolution study of the absorption rate and disposition kinetic values of lindane in sheep.

Absorption rate and plasma and fat disposition of lindane after various lindane percutaneous treatments in shorn and unshorn sheep were investigated. To analyze data with a deconvolution method, IV administration was performed to determine the basic pharmacokinetic values of lindane in sheep. After IV administration, the steady state volume of distribution was very high (8.07 +/- 3.60 L/kg of body weight), and the mean residence time was long (28.1 +/- 11.7 hours). Deconvolution analysis indicated that lindane absorption was continuous until 33 to 41 days after spraying with a 0.025% lindane solution. Total amount of absorbed lindane in shorn (15,171 +/- 4,463 micrograms/kg) sheep was about twice that in unshorn (7,615 +/- 3,128 micrograms/kg) sheep; from deconvolution analysis, it was calculated that the time required for 50% of the available dose to be absorbed was between 115 and 179 hours. After percutaneous lindane administration, the fat concentration was compared with the available lindane dose. The apparent half-life of lindane elimination in fat was 225 +/- 47.4 hours, which is similar to the value calculated for the absorption rate constant. By comparing fat and plasma concentrations, it was calculated that for a mean plasma concentration of 5 ng/ml, the fat lindane concentration was 1.65 +/- 0.87 micrograms/g (ie, lower than the generally accepted tolerance level of 2 micrograms/g).