Concentrations of tinidazole in gingival crevicular fluid and plasma in dogs after multiple dose administration

Tinidazole 15 mg/kg was administered to eight Beagle dogs with gingivitis or periodontitis twice daily for 3 days. Tinidazole concentrations in blood and gingival crevicular fluid (GCF) were measured 1,3,6 and 9 h after the morning dose each day. The concentration of tinidazole was determined by high performance liquid chromatography (HPLC). The mean concentration of tinidazole in GCF for each dog ranged from 6.05 to 9.32 αg/mL at different time points after the first dose, and on the first day the highest concentration was observed 6 h after the drug administration. Tinidazole concentrations were 34 ± 4%-72 ± 9% (mean ± SEM) of simultaneous plasma concentration. At steady-state, on the third treatment day, the mean tinidazole concentrations in GCF ranged from 6.68 to 13.1 μg/mL, i.e. 44 ± 6%-75 ± 25% of the corresponding concentrations in plasma. Tinidazole concentration in GCF exceeded the MIC values for putative path-ogenic periodontal bacteria and it is concluded that, when indicated, tinidazole could be used for chemotherapy of periodontitis in dogs.     

Pharmacokinetics of tinidazole in dogs and cats

Pharmacokinetics of tinidazole in dogs and cats after single intravenous (15 mg/kg) and oral doses (15 mg/kg or 30 mg/kg) were studied in a randomized crossover study. Tinidazole was completely absorbed at both oral dose levels in cats and dogs. Peak tinidazole concentration in plasma was 17.8 micrograms/ml in dogs and 22.5 micrograms/ml in cats after 15 mg/kg p.o. The oral dose of 30 mg/kg resulted in peak levels of 37.9 micrograms/ml in dogs and 33.6 micrograms/ml in cats. The apparent total plasma clearance of the drug was about twofold higher in dogs than in cats, resulting in an elimination half-life that was twice as long in cats (8.4 h) as in dogs (4.4 h). The apparent volume of distribution was 663 ml/kg in dogs and 536 ml/kg in cats. Therapeutic plasma drug concentrations higher than the MIC values of most tinidazole-sensitive bacteria were achieved for 24 h in cats and for 12 h in dogs after a single oral dose of 15 mg/kg. From the pharmacokinetic standpoint tinidazole seems to be well-suited to clinical use in small animal practice.     

Preliminary pharmacokinetic study of isometamidium chloride in camels

Isometamidium chloride was given to camels at a single intravenous dose rate of 0.5 or 1 mg kg-1 and the plasma drug concentration measured spectrophotometrically at frequent intervals for up to 48 hours. Isometamidium chloride concentrations were found to be 9.8 +/- 0.2 and 8.7 +/- 0.2 micrograms ml-1 half an hour after treatment with 1 and 0.5 mg kg-1, respectively, and 1.7 +/- 0.3 and 0.7 +/- 0.3 micrograms ml-1 after 24 hours. No measurable drug concentration was found 48 hours after dosing.     

Furazolidone concentrations in plasma, milk and some tissues of Nubian goats

The concentrations of furazolidone (FZ) in plasma and milk were measured in goats treated orally with the drug at a dose of 10 mg kg-1 daily for 5 days. The maximum plasma concentrations obtained were 1.57 +/- 0.52 micrograms ml-1 (n = 5) 8 h after the first dose, and 2.13 +/- 0.11 micrograms ml-1 (n = 4) 6 h after the fifth dose. The maximum milk concentration was 0.88 +/- 0.32 micrograms ml-1 (n = 4) 8 h following the administration of a single dose. Using a colorimetric method, FZ was not detectable in goats' liver or muscle after the recommended therapeutic dose (10 mg kg-1, 5 days). However, using an HPLC method, the drug was detected 24 h after the treatment in the gluteal muscle and liver at concentrations of 0.26 +/- 0.01 microgram g-1 (n = 5) and 0.10 +/- 0.02 microgram g-1 (n = 5), respectively. The drug concentrations decreased significantly (P less than 0.05-0.01) at 3, 5 and 7 days after treatment, and no measurable concentrations were found after 10 days.     

Plasma cortisol response to ketoconazole administration in dogs with hyperadrenocorticism

The effect of orally administered ketoconazole on plasma cortisol concentration in dogs with hyperadrenocorticism was evaluated. Every 30 minutes from 0800 hours through 1600 hours and again at 1800 hours, 2000 hours, and 0800 hours the following morning, 15 clinically normal dogs and 49 dogs with hyperadrenocorticism had plasma samples obtained and analyzed for cortisol concentration. The mean (+/- SD) plasma cortisol concentration for the initial 8-hour testing period was highest in 18 dogs with adrenocortical tumor (5.3 +/- 1.6 micrograms/dl), lowest in 15 control dogs (1.3 +/- 0.5 micrograms/dl), and intermediate in 31 dogs with pituitary-dependent hyperadrenocorticism (PDH; 3.4 +/- 1.2 micrograms/dl). Results in each of the 2 groups of dogs with hyperadrenocorticism were significantly (P less than 0.05) different from results in control dogs, but not from each other. The same cortisol secretory experiment was performed, using 8 dogs with hyperadrenocorticism (5 with PDH; 3 with adrenocortical tumor) before and after administration at 0800 hours of 15 mg of ketoconazole/kg of body weight. Significant (P less than 0.05) decrease in the 8-hour mean plasma cortisol concentration (0.9 +/- 0.2 microgram/dl) was observed, with return to baseline plasma cortisol concentration 24 hours later. Twenty dogs with hyperadrenocorticism (11 with PDH, 9 with adrenocortical tumor) were treated with ketoconazole at a dosage of 15 mg/kg given every 12 hours for a half month to 12 months. The disease in 2 dogs with PDH failed to respond to treatment, but 18 dogs had complete resolution of clinical signs of hyperadrenocorticism and significant (P less than 0.05) reduction in plasma cortisol responsiveness to exogenous adrenocorticotropin (ACTH).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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)     

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.     

Altered disposition of propylthiouracil in cats with hyperthyroidism

The oral and intravenous disposition of the anti-thyroid drug propylthiouracil (PTU) was determined in six clinically healthy cats and four cats with naturally occurring hyperthyroidism. Compared with the normal cats, the mean plasma elimination half-life of PTU was significantly (P less than 0.001) shorter in the hyperthyroid cats (77.5 +/- 5.8 minutes compared with 125.5 +/- 3.7 minutes) and the total body clearance of PTU was significantly (P less than 0.05) more rapid in the cats with hyperthyroidism (5.1 +/- 0.8 ml kg-1 min-1 compared with 2.7 +/- 0.2 ml kg-1 min-1). Following oral administration, both the bioavailability (59.7 +/- 4.9 per cent compared with 73.3 +/- 3.7 per cent) and peak plasma concentrations (14.5 +/- 1.6 micrograms ml-1 compared with 18.9 +/- 0.9 micrograms ml-1) of PTU were significantly (P less than 0.05) lower in the hyperthyroid cats than in the control cats. No difference was noted, however, between the apparent volume of distribution for PTU in the two groups of cats. Overall, results of this study indicate that the oral bioavailability of PTU is decreased and PTU disposition is accelerated in cats with hyperthyroidism.     

Oxytetracycline pharmacokinetics, tissue depletion, and toxicity after administration of a long-acting preparation at double the label dosage

Oxytetracycline (OTC) concentration in plasma and tissues, plasma pharmacokinetics, depletion from tissue, and toxicity were studied in 30 healthy calves after IM administration of a long-acting OTC preparation (40 mg/kg of body weight) at double the label dosage (20 mg/kg). Plasma OTC concentration increased rapidly after drug administration, and by 2 hours, mean (+/- SD) values were 7.4 +/- 2.6 micrograms/ml, Peak plasma OTC concentration was 9.6 +/- 2.6 micrograms/ml, and the time to peak plasma concentration was 7.6 +/- 4.0 hours. Plasma OTC concentration decreased slowly for 168 hours (elimination phase) after drug administration, and the elimination half-life was 23.9 hours. Plasma OTC concentration exceeded 3.8 micrograms/ml at 48 hours after drug administration. From 168 to 240 hours after drug administration, plasma OTC concentration decreased at a slower rate than that seen during the elimination phase. This slower phase was termed the depletion phase, and the depletion half-life was 280.7 hours. Tissue OTC concentration was highest in kidneys and liver. Lung OTC concentration exceeded 4.4 micrograms/g of tissue and 2.0 micrograms/g of tissue at 12 and 48 hours after drug administration, respectively. The drug persisted the longest in kidneys and liver. At 42 days after drug administration, 0.1 micrograms of OTC/g of kidney was detected. At 49 days after drug administration, all OTC tissue concentrations were below the detectable limit. Reactions and toxicosis after drug administration were limited to an anaphylaxis-like reaction (n = 1) and injection site swellings (n = 2).     

Effect of probenecid on disposition kinetics of ampicillin in horses.

The effect of an oral dose of probenecid on the disposition kinetics of ampicillin was determined in four horses. An intravenous bolus dose (10 mg/kg) of ampicillin sodium was administered to the horses on two occasions. On the first occasion the antibiotic was administered on its own, and on the second occasion it was administered one hour after an oral dose of 75 mg/kg probenecid. The plasma concentration of probenecid reached a mean (+/- se) maximum concentration (Cmax) of 188-6 +/- 19.3 micrograms/ml after 120.0 +/- 21.2 minutes and concentrations greater than 15 micrograms/ml were present 25 hours after it was administered. The disposition kinetics of ampicillin were altered by the presence of probenecid and as a result the antibiotic had a slower body clearance (ClB; 109.4 +/- 6.71 ml/kg hours compared with 208.9 +/- 26.2 ml/kg hours) a longer elimination half-life (t1/2 beta 1.198 hours compared with 0.701 hours) and consequently a larger area under the plasma concentration versus time curve (AUC 92.3 +/- 5.09 mg/ml hours compared with 35.95 +/- 3.45 mg/ml hours) when compared with animals to which ampicillin was administered alone. The ampicillin concentrations observed suggest that the dosing interval for horses may be increased from between six and eight hours to 12 hours when probenecid is administered in conjunction with the ampicillin.     

Liver function tests in dogs with portosystemic shunts: measurement of serum bile acid concentration

Sulfobromophthalein excretion and plasma ammonia and serum bile acid concentrations were measured in 11 dogs with portal vascular anomalies. The fasting serum bile acid concentration was increased in all 11 dogs (78.9 +/- 16.1 mumol/L; normal, 2.6 +/- 0.4 mumol/L). For values measured in 8 dogs, the 2-hour postprandial serum bile acid concentration was increased further (177.0 +/- 26.4 mumol/L; normal, 7.6 +/- 2.3 mumol/L). The fasting plasma ammonia concentration was markedly increased in all 11 dogs (246.9 +/- 40.3 micrograms/dl; normal, 27 to 15 micrograms/dl). Thirty minutes after the oral administration of ammonium chloride, the plasma ammonia concentration was increased further in the 7 dogs (510.7 +/- 45.5 micrograms/dl; normal, 57.5 to 20.5 micrograms/dl). Results of the sulfobromophthalein excretion test were abnormal in 10 of 11 dogs (12.3 +/- 1.4%; normal, less than 5% retention after 30 minutes).     

HPLC determination and pharmacokinetics of thiabendazole and its major metabolite 5-OH thiabendazole in equine plasma

Separate high performance liquid chromatographic methods were developed for thiabendazole (TBZ) and 5-hydroxy thiabendazole (5-OH-TBZ) determination in horse plasma using 1-methyl-2-phenyl benzimidazole (MPBZ) as an internal standard. In both methods TBZ and 5-OH-TBZ were extracted from plasma using organic solvents, injected on to a C-18 column, and eluents monitored by a fluorescence detector. However, mobile phase composition, extraction solvent as well as detector wavelength differed in the two methods. The linear range for TBZ was 0.02 to 0.77 microgram ml-1 while that for 5-OH-TBZ was 0.96 to 8.0 micrograms ml-1. A commercially available TBZ oral suspension was administered to four thoroughbred horses in the following manner: days 1 and 2, 44 mg kg-1; days 4 and 5, 440 mg kg-1. Blood samples were collected during the 24 hours after administration and then analysed for TBZ and 5-OH-TBZ. Half-lives (t1/2), maximum plasma concentrations (Cmax), area under plasma concentration time curves (AUC O-alpha), and relative apparent bioavailability (F), were determined using pharmacokinetic equations. The pharmacokinetic parameters varied in the following manner: 1.16 to 13.63 hours (t1/2), 12 to 131 micrograms ml-1 X hours (AUC O-alpha), 3.33 to 8.90 micrograms ml-1 (Cmax), 1.38 to 0.12 (F) after 44 mg kg-1 and 440 mg kg-1 doses, respectively. The ratios of concentrations of TBZ to 5-OH-TBZ after oral administration of TBZ, were significantly lower for 44 mg kg-1 than 440 mg kg-1 doses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of ceftazidime in sheep and its penetration into tissue and peritoneal fluids

Serum, tissue and peritoneal fluid concentrations of ceftazidime were studied in ewes after intravenous, intramuscular and subcutaneous administration at 50 mg kg-1 bodyweight. Tissue and peritoneal cages were implanted in the animals studied. After intravenous bolus administration, the mean serum concentration versus time profile was best described by a two-compartment open model. The distribution rate constant (alpha) was 3.5 +/- 1.1 h-1 and the half-life (t 1/2 alpha) 0.22 +/- 0.09 hour. The elimination rate constant (beta) was 0.43 +/- 0.04 h-1 and half-life (t 1/2 beta) 1.6 +/- 0.2 hours. The area under the curve was 275.7 +/- 84.0 micrograms.ml-1 h. The volume of distribution as steady state was 356.1 +/- 208.0 ml kg-1. The penetration ratio into tissue fluid was 62.6 +/- 15.1 per cent and into peritoneal fluid 61.1 +/- 16.5 per cent. After intramuscular injection, the elimination half-life was 1.7 +/- 0.2 hours, the area under the curve was 228.7 +/- 43.3 micrograms.ml-1 h. and the elimination rate constant was 0.42 +/- 0.05 h-1. The penetration ratio into tissue fluid was 68.5 +/- 37.3 per cent and into peritoneal fluid 73.3 +/- 34.4 per cent. After subcutaneous injection, the elimination half-life was 1.8 +/- 0.5 hours, the area under the curve was 231.8 +/- 65.6 micrograms.ml-1 h. and the elimination constant was 0.41 +/- 0.10 h-1. The penetration ratio into tissue fluid was 47.2 +/- 3.5 per cent and into peritoneal fluid 58.1 +/- 15.6 per cent.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunoreactive N-terminal fragment of proatrial natriuretic peptide, ANP (1–98), in plasma of healthy dogs and dogs with impaired volume regulation: a comparison with the C-terminal ANP (99–126)

Atrial natriuretic peptide (ANP) is stored in atrial myocytes as a 126 amino acid precursor molecule (ANP 1-126) and is cleaved during its release into circulation into the biologically active C-terminal ANP (99-126) and the N-terminal counterpart, ANP (1-98). While interest has focused on ANP (99-126) under physiological and pathophysiological conditions, data for the cosecreted N-terminal sequence, ANP (1-98) are generally missing. Plasma levels of the N-terminal immunoreactive peptide (N-ANP [1-98]) were measured in normal dogs, and in dogs with impaired volume regulation (congestive heart failure; chronic renal failure or Cushing's syndrome and compared with those of C-ANP (99-126). The N-ANP (1-98) concentration was 593.1 +/- 81.1 fmol ml-1 in normal subjects, which is about 60-fold higher than the C-ANP (99-126) (10.8 +/- 2.6 fmol ml-1). In patients suffering from chronic renal failure ANP (1-98) was increased to 1582 +/- 196 fmol ml-1, and in dogs with congestive heart failure to 1612 +/- 244 fmol ml-1. In contrast, Cushing's syndrome dogs showed decreased N-ANP (1-98) concentrations (351 +/- 65.9 fmol ml-1). There was a positive correlation between plasma levels of N-ANP (1-98) and C-ANP (99-126) levels (correlation coefficients: normal: r = 0.78; congestive heart failure: r = 0.76; chronic renal failure: r = 0.86; Cushing's syndrome: r = 0.57). High pressure liquid chromatographic analysis of dog plasma showed one major peak of N-terminal immunoreactivity corresponding to ANP (1-98).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics and local tolerance of a long-acting oxytetracycline formulation in camels.

Disposition and local tolerance of a new oxytetracycline (OTC) long-acting formulation were evaluated in camels by measuring the dynamics of creatine kinase. Six camels (Camelus dromedarius) were administered OTC by IV and IM routes according to a 2-period cross-over, study design. Serum OTC concentration was measured, using a microbiological assay procedure. After IV administration (5 mg/kg of body weight), mean residence time was 7.7 +/- 2.8 hours, steady-state volume distribution was 706.1 +/- 168.6 ml.kg-1 and serum clearance was 75.3 +/- 23.2 ml.kg-1.h-1. After IM administration of the long-acting OTC formulation (10 mg/kg), maximal OTC concentration (3.49 +/- 0.44 micrograms.ml-1) was observed after 7.3 +/- 3.5 hours; the mean systemic availability was near 100%, and serum concentration greater than 0.5 micrograms.ml-1 was maintained for about 72 hours. After IM administration, mean control serum activity of creatine kinase was multiplied by a factor of 3.36 +/- 1.55; at 72 hours after OTC administration, the serum creatine kinase activity returned to control values. It was concluded that OTC is an antibiotic of potential interest in camels and that a dosage regimen of 10 mg.kg-1 deserves attention when using a long-acting formulation that has good local tolerance and near total systemic availability.     

Comparison of pharmacokinetic variables for two injectable formulations of netobimin administered to calves

In a 4 x 4 crossover-design study, pharmacokinetic variables of 2 injectable formulations of netobimin (trisamine salt solution and zwitterion suspension) were compared after SC administration in calves at dosage of 12.5 mg/kg of body weight. Netobimin parent drug was rapidly absorbed, being detected between 0.25 and 12 hours after treatment, with maximal plasma drug concentration (Cmax) values of 2.20 +/- 1.03 micrograms/ml achieved at 0.75 +/- 0.19 hour (trisamine) and 1.37 +/- 0.59 micrograms/ml at 0.81 +/- 0.18 hour (zwitterion). Netobimin area under the plasma concentration-time curve (AUC) was 7.59 +/- 3.11 micrograms.h/ml (trisamine) and 6.98 +/- 1.60 micrograms.h/ml (zwitterion). Elimination half-life (t1/2 beta) was 2.59 +/- 0.63 hours (trisamine) and 3.57 +/- 1.45 hours (zwitterion). Albendazole was not detected at any time. Albendazole sulfoxide was detected from 4 hours up to 20 hours (trisamine) and from 6 hours up to 24 hours (zwitterion) after administration of the drug. The Cmax values were 0.48 +/- 0.16 micrograms/ml and 0.46 +/- 0.26 micrograms/ml for trisamine and zwitterion formulations, respectively, achieved at time to peak drug concentration (Tmax) values of 9.50 +/- 1.41 hours (trisamine) and 11.30 +/- 1.04 hours (zwitterion). Albendazole sulfoxide AUC was 3.86 +/- 1.04 micrograms.h/ml (trisamine) and 4.40 +/- 3.24 micrograms.h/ml (zwitterion); t1/2 beta was 3.05 +/- 0.75 hours (trisamine) and 3.90 +/- 1.44 hours (zwitterion). Albendazole sulfone was detected from 4 (trisamine) or 6 hours (zwitterion) to 24 hours after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics and bioavailability of spiramycin in pigs.

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

Pharmacokinetic profile of cefotaxime in goats

Cefotaxime was administered to goats intravenously, intramuscularly and subcutaneously to determine blood and urine concentration, kinetic behaviour and bioavailability. Following a single intravenous injection, the blood concentration-time curve indicated a two compartment open model, with an elimination half-life value (t1/2 beta) of 22.38 +/- 0.41 minutes. Both intramuscular and subcutaneous routes showed slower values, that is, 38.64 and 69.58 minutes. The apparent volume of distribution of cefotaxime in goats was less than 1 litre kg-1 and suggested a lower distribution in tissues than in blood. After intramuscular and subcutaneous injections peak plasma cefotaxime concentrations were 77.8 +/- 1.7 and 44.0 +/- 0.8 micrograms ml-1 at 29.6 and 40.4 minutes, respectively. The average bioavailability of cefotaxime given by intramuscular and subcutaneous injection was 1.08 and 1.25 times the intravenous availability, respectively. The cefotaxime concentration remained in urine 24 hours longer after subcutaneous injection than after intramuscular administration.     

Serum concentrations of thyroxine and 3,5,3'-triiodothyronine before and after intravenous or intramuscular thyrotropin administration in dogs

Response to thyrotropin (TSH) was evaluated in 2 groups of mixed-breed dogs. Thyrotropin (5 IU) was administered IV to dogs in group 1 (n = 15) and IM to dogs in group 2 (n = 15). Venous blood samples were collected immediately before administration of TSH and at 2-hour intervals for 12 hours thereafter. In group 1, the maximum mean concentration (+/- SD) of thyroxine (T4; 7.76 +/- 2.60 micrograms/dl) and 3,5,3'-triiodothyroxine (T3; 1.56 +/- 0.51 ng/ml) was attained at postinjection hours (PIH) 8 and 6, respectively. However, the mean concentration of T4 at PIH 6 (7.21 +/- 2.39 micrograms/dl) was not different (P greater than 0.05) from the mean concentration at PIH 8. The maximum mean concentration of T4 (10.10 +/- 3.50 micrograms/dl) and T3 (2.22 +/- 1.24 ng/ml) in group 2 was attained at PIH 12 and 10, respectively. Because dogs given TSH by the IM route manifested pain during injection, had variable serum concentrations of T3 after TSH administration, and may require 5 IU to achieve maximal increases in serum T4 concentrations, IV administration of TSH is recommended. The optimal sampling time to observe maximal increases in T3 and T4 after IV administration of TSH was 6 hours. Repeat IV administration of TSH may cause anaphylaxis and, therefore, is not recommended.