Pharmacokinetics of doxycycline in dogs.

Six adult dogs were given doxycycline hyclate at a dosage of 5 mg/kg of body weight intravenously so that pharmacokinetic parameters could be evaluated. Serum doxycycline concentrations were determined over a 48 h period using a modified agar well bioassay. Compartmental pharmacokinetic evaluation of the serum concentration time data indicated that doxycycline has a half-life of 10.36 h, a body clearance of 1.68 +/- 0.44 mL/min/kg, and a volume of distribution at steady state of 1.468 +/- 0.237 L/kg. Doxycycline pharmacokinetics are favorable for therapeutic use in the dog.

Compartmental and noncompartmental pharmacokinetic analyses of minocycline hydrochloride in the dog.

Six adult dogs were given 5 mg of minocycline hydrochloride/kg of body weight IV. Pharmacokinetic evaluation of the serum drug concentration versus time data was performed, using the 2-compartment open model, the 3-compartment open model, and a noncompartmental model involving use of the statistical moment theory. All pharmacokinetic values except clearance were model independent. Minocycline half-life ranged between 6.48 and 7.24 hours; volume of distribution at steady state, between 1.859 +/- 0.368 and 2.001 +/- 0.468 L/kg; and clearance, between 3.195 +/- 0.618 and 3.424 +/- 0.684 ml/min/kg. These data are similar to those reported for oxytetracycline and indicate that the frequency of administration of the 2 tetracyclines should be the same. Three of the 6 dogs developed an adverse response to the IV injection of minocycline. Dog 1 developed urticaria and had initial serum drug concentrations of approximately 2 times the mean concentrations for the other dogs; values were not included in the pharmacokinetic analysis. Two other dogs had transient signs indicating cardiovascular depression or hypotension; their data were included. Due to the frequency of the unexpected reactions found in this study, it was concluded that dogs should not be given minocycline rapidly IV.

Influence of endotoxin-induced fever on the pharmacokinetics of gentamicin in ewes.

The pharmacokinetics of gentamicin (3 mg/kg of body weight) were evaluated in 6 adult ewes before and after fever was induced with Escherichia coli endotoxin (1 micrograms/kg). In the ewes with normal rectal temperature, significant (P less than 0.05) increases in rectal temperature occurred before gentamicin injection and during the first 2 hours. Other mild clinical signs of fever also were present. In the same ewes with endotoxin-induced fever, statistically (P less than 0.05) increased gentamicin concentrations occurred at 15 and 40 minutes and at 6 hours after injection of gentamicin. Changes were not observed in the apparent volume of distribution calculated by the area method, the volume of distribution at steady state, the overall biological half-life, or body clearance. Significant (P less than 0.05) reductions occurred in the zero time intercept for distribution, the distribution rate constant, the concentration in plasma at time of injection, the volume of the peripheral compartment, and the first order transfer rate constants; only the volume of the central compartment was increased. Total amounts of gentamicin were increased in the central compartment and decreased in the peripheral or tissue compartment.

Serum erythromycin concentration in sheep fed two diets.

Serum erythromycin concentrations following a single IV injection (12.5 mg/kg) were compared in 6 sheep during feeding of a grass hay diet and a concentrate diet. The concentrate diet resulted in a mean decrease of at least 1 pH unit in forestomach fluid, but did not significantly alter either the serum drug concentrations or half-life. Variable antibacterial activity was present in forestomach fluid as early as 1 or 2 hours after injection. This study indicates that ion-trapping in forestomach fluid as a result of normal dietary changes does not require therapeutic dosage adjustment.

Hepatitis in a dog given sulfadiazine-trimethoprim and cyclophosphamide.

Vomiting, diarrhea, icterus and elevated serum alkaline phosphatase, SGPT and serum bilirubin levels occurred in a 12-year-old Basenji on sulfadiazine-trimethoprim and cyclophosphamide therapy. After use of the antibacterial drug was discontinued, the dog returned to normal with no further evidence of hepatocellular damage.

Effects of promethazine on hemorrhagic shock in the dog.

The effects of pre- and post-treatment with promethazine, an antihistamine, in hemorrhage-shocked dogs were investigated. Survival to 6 hours was enhanced in the dogs given (IM administration) the H1-receptor antagonist at 1 hour before hemorrhage was induced when compared with survivals of saline-treated control dogs (3 of 5 dogs vs 1 of 5 dogs). Furthermore, 4 of 5 dogs given (IV administration) promethazine at 30 minutes after the initial hemorrhage survived. Promethazine treatment by either route increased mean arterial pressure among surviving dogs throughout the 6-hour experimental period.

Effect of hypocalcemia on motility of the ruminant stomach.

The sensitivity of ruminal and abomasal contractions to hypocalcemia was evaluated in sheep. Serum diffusible calcium concentrations were determined during induction of hypocalcemia (IV infusion of Na2EDTA) and recovery from hypocalcemia (no infusion). Contractile strength of the rumen gradually decreased as serum diffusible calcium concentrations decreased; significant correlation (r = 0.75; P less than 0.001) was observed. Ruminal contractions disappeared before clinical signs of hypocalcemia were seen. Abomasal contractions were slightly reduced when serum diffusible calcium concentrations were equal to those producing ruminal stasis and clinical signs of hypocalcemia. These observations indicated that ruminal dysfunction may occur considerably before the onset of clinical signs of hypocalcemia.

Determination of blood pressure by indirect methods in dogs given acetylpromazine maleate.

This study was designed to monitor and compare indirect blood pressures by two methods (ultrasonic Doppler and photoelectric) after intravenous acetylpromazine maleate at three different doses (0.11, 0.55, and 1.10 mg/kg). Sixteen unanesthetized dogs were placed in right lateral recumbency and pressures estimated from the left hind leg at two preinjection times and at 3, 15, 60 and 120 minutes postinjection. This procedure was followed for each dog for each of the three doses. Preinjection ultrasonic mean values and standard deviations were similar to published values. Photoelectric systolic pressures were lower and diastolic pressures higher than ultrasonic systolic and diastolic pressures. The decrease in blood pressure was detected by both methods. Neither method revealed a dose related response.

Effects of neomycin on the waveform of auditory-evoked brain stem potentials in dogs.

Neomycin sulfate was administered intravenously to eight mixed-breed dogs at a dosage of 30 mg/kg/day for as long as 50 days. Auditory-evoked brain stem potentials (AEBP) were recorded from the dogs three times a week. The AEBP amplitudes and latencies from the eight treated and the eight control dogs were compared. All treated dogs eventually exhibited an isoelectric AEBP. The time required for the AEBP waveform loss to occur in the treated dogs varied between 22 and 50 days. The AEBP waveforms were still isoelectric when measured as long as 150 days after neomycin administration was stopped. The fact that AEBP did not return would tend to support the findings of others that the loss of the receptors in the inner ear, due to neomycin toxicity, is permanent. The results of this electrophysiologic study indicate that the organ of Corti (organum spirale) is the site of pathologic changes in the auditory system that result from neomycin treatment.

Toxicity and bioaccumulation of pentachlorophenol in broiler chickens.

Hubbard-Hubbard broiler chickens were fed graded levels (0, 1, 10, 100, and 1000 ppm) of pentachlorophenol (PCP) containing less than .0023% octachlorodibenzo-p-dioxin (OCDD) for 8 weeks. Tissue samples for PCP, OCDD, and pentachloroanisole (PCA) were cleaned up via gel permeation chromatography and analyzed by gas chromatography employing electron capture detection. Kidney weights were significantly increased by the 100 ppm and 1000 ppm PCP diet. Weights of all other organs including the body weights were significantly lowered by the 1000 ppm PCP diet. Except for the control group, histopathologic examination of the liver revealed bile duct proliferation and some fatty changes in all of the 6-week-old birds. Examination of the brain, liver, gizzard, pancreas, intestine, proventriculus, spleen, kidney, lung, and heart revealed no histopathological lesions in the treated or control birds. Significant linear relationships were found between PCP accumulation in tissues and the concentration of dietary PCP. Accumulation of PCP was greatest in the kidney followed by liver, heart, leg, breast, gizzard, and fat. The high residue levels in the kidney and liver may reflect principal routes of elimination and metabolism. Following a 5 week withdrawal of PCP from the diet, PCP residues were still present in the adipose tissue of all treated birds. Residue levels in the kidney and liver were reduced at the first and third week of withdrawal, but a continuous decline was interrupted by a slight elevation in residue level at the fifth week of withdrawal from the chemical.

Tissue residues from feeding pentachloronitrobenzene (quintozene) to White Leghorn chickens.

One-day-old White Leghorn chicks were fed graded levels (0, 10, 50, 100 and 1,000 ppm) of pentachloronitrobenzene (PCNB; quintozene) up to 8 weeks. Each treatment group consisted of 90 randomly selected birds (2 replications of 45 birds each). Body weight gains were significantly lower at the 1,000-ppm treatment level. Histopathologic examination of brain, liver, pancreas, small intestine, gizzard, spleen, kidney, lung, and heart failed to reveal lesions in either control or treated groups. Bioaccumulation of PCNB or its metabolites (pentachloroaniline and pentachlorophenylmethylsulfide) in tissues only occurred in trace or very low concentrations. However, trace contaminating of PCNB, eg, hexachlorobenzene (HCB) and pentachlorobenzene (PCB) accumulated in tissues to a significant degree. Tetrachloronitrobenzene, another contaminant of PCNB, was found in only the adipose and cardiac tissues following the feeding of 1,000 ppm PCNB. Storage of PCNB, HCB, and PCB in adipose and other tissues was linearly related to the amount of PCNB in the ration.

Endotoxin absorption in hay-fed and lactic acidotic sheep.

Absorption of endotoxin from the gastrointestinal tract was evaluated in hay-fed and lactic acidotic sheep duodenally infused with 10 mg of Escherichia coli endotoxin, and in lactic acidotic sheep not infused. The effect of abomasal fluid on biological activity of endotoxin was also evaluated. Leukopenia was the criterion used for detecting endotoxemia. Absorption of endotoxin from the gastrointestinal tract was not detected in either hay-fed or lactic acidotic sheep. Endotoxin appeared to maintain its activity after incubation with abomasal fluid, and the presence of endogenous endotoxin in abomasal contents was indicated. The results indicate that endotoxin of alimentary origin may not be involved in the lactic acidosis syndrome in ruminants.

The accumulation and elimination of tissue residues after feeding pentachloronitrobenzene to White Leghorn cockerels.

Day-old White Leghorn cockerels were fed graded levels (10, 50, 100, and 1000 ppm) of pentachloronitrobenzene (PCNB) containing pentachlorobenzene (PCB), tetrachloronitrobenzene (TCNB), and hexachlorobenzene (HCB) at trace contaminants, for 12 weeks. Bioaccumulation of PCNB and its metabolites in tissues does not appear to occur to any major extent. The contaminants of PCNB, HCB, and PCB were found to accumulate to a greater degree in adipose tissue than does PCNB itself. TCNB was also detected in adipose tissue and in trace amounts in other tissues. PCNB accumulated to the highest concentration in body fat followed by gizzard and kidney. Only traces of PCNB were found in heart, liver, leg, and heart muscle. Metabolites, pentachloroaniline (PCA), and pentachlorphenylmethylsulfide (PCMS) were found in only trace quantities following the feeding of 1000 ppm PCNB. Half-life values for the depletion of the contaminants of PCNB, PCB, and HCB were determined in adipose tissue of cockerels; values as high as 53 and 95 days were found for PCB and HCB, respectively.

Effect of ruminal lactic acid-utilizing bacteria on adaptation of cattle to high-energy rations.

Heifers, unadapted to a concentrate ration, were intraruminally inoculated (1 dose) with cultures of ruminal lactic acid-utilizing bacteria or with ruminal fluid from a steer adapted to a concentrate ration. Inoculation with cultures (1 L) of Selenomonas ruminantium or Megasphaera elsdenii did not produce better average daily weight gains or feed efficiency of heifers fed a high-energy ration for 21 days, if these values were compared with the performance of noninoculated heifers. Average daily weight gain and feed efficiency of heifers inoculated with 1 L of Peptococcus asaccharolyticus culture or with 1 L of adapted ruminal fluid and fed a high-energy ration for 21 days were better if these values were compared with the performance of noninoculated heifers.

Residues in broiler chickens fed low levels of hexachlorobenzene.

Male broiler chicks (Hubbard-Hubbard) were fed graded levels (0, 0.0006, 0.006, 0.03, and 0.120 p.p.m.) of hexachlorobenzene (HCB) for 8 weeks. Gel permeation chromatography was used to prepare tissue samples from fat, heart, gizzard, leg muscle, breast muscle, kidney, and liver for analysis by gas-liquid chromatography employing electron capture detection. No treatment related trends could be determined for body or organ weights. Histopathologic examination of brain, liver, testes, pancreas, small intestine, ventriculus, spleen, kidney, lung, and heart failed to reveal lesions in either control or treated groups. A linear relationship was found between HCB accumulation in tissues and the dietary HCB level. HCB accumulation was greatest in adipose tissue followed by the heart, gizzard, leg, kidney, liver, and breast. The biomagnification of HCB in adipose tissue of broiler chickens was 11 to 18 times the concentration in the diet. For example, a concentration of 0.03 p.p.m. of HCB in the diet resulted in the accumulation of HCB in adipose tissue in excess of 0.5 p.p.m. After 7 weeks, birds were taken off rations containing HCB. After a withdrawal period of five weeks, 0.5 p.p.m. of HCB remained in adipose tissue of birds that had been fed 0.12 p.p.m. of HCB.

Studies of mechanisms of action of secretin and pancreozymin on rumen motility.

Rapid intravenous administration of a single bolus of secretin caused a marked decrease in both amplitude and frequency of rumen contractions, whereas pancreozymin administration caused a decrease in frequency but an increase in amplitude of rumen contractions. Alpha receptor blockade with phenoxybenzamine or beta receptor blockade with propranolol did not alter secretin or pancreozymin effects on rumen motility. Blockade of histamine receptor sites with tripelennamine did not prevent the secretin-induced decrease of rumen motility. A marked similarity in the decreased rumen motility pattern was observed when secretin effects were compared to aminophylline effects.

Lactic acid-utilizing bacteria in ruminal fluid of a steer adapted from hay feeding to a high-grain ration.

A mature, rumen-cannulated steer fed Coastal Bermuda grass hay for 8 weeks was adapted to a high-grain ration by stepwise increases in grain over a period of 4 weeks. The grain rations had concentrate-to-roughage ratios of 40:60, 70:30, and 85:15 and were fed for 10, 7, and 11 days, respectively. Numerical estimates of lactate-utilizing bacteria in ruminal fluid of the steer the last 3 days each ration was fed were made by colony counts. Lactate-utilizing bacteria were identified as Megasphaera elsdenii, Peptococcus asaccharolyticus, and Selenomonas ruminantium. Maximal numbers of lactate-utilizing bacteria were observed in the ruminal fluid of the steer during feeding the concentrate-to-roughage ration of 70:30.

Periovulatory changes in peripheral plasma progesterone and estrogen concentrations in the mare.

Concentrations of progesterone and estrogen were measured in peripheral blood plasma samples from mares around the time of ovulation. Samples were collected every 2 hours from 36 hours before, to 26 hours after, ovulation and assayed by radioimmunoassay. Progesterone concentrations were between 60 and 100 pg/ml for the period 24 hours before ovulation through 8 hours after ovulation. By 10 hours after ovulation, concentrations increased to 140 pg/ml and, by 26 hours after ovulation, reached 346 pg/ml. Plasma estrogen concentrations did not change significantly throughout the same period.