The effect of induced fever on the biokinetics of norfloxacin and its interaction with probenecid in goats

The kinetic profiles of norfloxacin were evaluated in afebrile, febrile and probenecid pre-treated (70 mg/kg orally) febrile goats after a single intravenous (i.v) dose (5 mg/kg). Fever was induced and maintained for 12 h by injecting Escherichia coli endotoxin (0.2 g/kg, i.v.) and repeating it in half the dose (0.1 g/kg) 5 h later. The plasma pharmacokinetic values for norfloxacin were best represented using a two-compartment open model. The peak norfloxacin plasma level of 90.52±3.18 g/ml attained in the probenecid pre-treated febrile goats was higher than that in the febrile (75.46±0.72 g/ml) or afebrile goats (62.25±1.23 g/ml). Cl_B and K _el values were significantly (p<0.01) decreased in febrile compared with afebrile goats. These values were further reduced in febrile goats after probenecid pre-treatment. However, t _1/2 was not affected by the fever-probenecid interaction. Norfloxacin may be used as an infusion with probenecid in caprine diseases where very high plasma levels are required to combat resistant organisms such as Bacteroides.Abbreviations MIC minimum inhibitory concentration - LPS lipopolysaccharide - i.v. intravenous(ly)     

Endotoxin in the conscious piglet: Its effects on some general and gastrointestinal myoelectrical parameters

The effect of an intravenous bolus injection of endotoxin, 0.1, 1 or 10 g/kg, on rectal temperature, clinical appearance, haematological parameters, and on gastrointestinal electrical activity was examined in 11 conscious piglets of 4–5 weeks of age, with implanted electrodes in the antrum pylori, duodenum, jejunum and ileum. All doses resulted in a significant and dose-dependent increase in rectal temperature, in pronounced clinical signs and in distinct changes in haematological values. These included shivering, depression, respiratory distress, a leukopenia (0.1 g/kg) or a leukocytosis (1 g/kg) with a shift to the left, an accelerated sedimentation rate and a decreased packed cell volume. Doses of 1 and 10 g/kg induced a transient inhibition of gastroduodenal electrical activity. These results suggest that, in the piglet, endotoxin primarily manifests general clinical signs and that the gastrointestinal effects coincide with these.     

Pharmacokinetics of Enrofloxacin and Its Metabolite Ciprofloxacin after Intramuscular Administration of Enrofloxacin in Goats

The pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were investigated in goats after a single intramuscular administration of enrofloxacin at 2.5 mg/kg body weight. The plasma concentrations of enrofloxacin and ciprofloxacin were determined simultaneously by a HPLC method. The peak concentrations (C _max) of enrofloxacin (1.13 g/ml) and ciprofloxacin (0.24 g/ml) were observed at 0.8 and 1.2 h, respectively. The elimination half-life (t _1/2), volume of distribution (V _d(area)), total body clearance (Cl_B) and mean residence time (MRT) of enrofloxacin were 0.74 h, 1.42 L/kg, 1329 ml/h per kg and 1.54 h, respectively. The t _1/2, area under the plasma concentration–time curve (AUC) and the MRT of ciprofloxacin were 1.38 h, 0.74 g h/ml and 2.73 h, respectively. The metabolic conversion of enrofloxacin to ciprofloxacin was appreciable (36%) and the sum of the plasma concentrations of enrofloxacin and ciprofloxacin was maintained at or above 0.1 g/ml for up to 4 h. Enrofloxacin appears to be useful for the treatment of goat diseases associated with pathogens sensitive to this drug.     

Tolerance to the Nephrotoxic Component of Narthecium ossifragum in Sheep: The Effects of Repeated Oral Doses of Plant Extracts

Young adult sheep were dosed with extracts of Narthecium ossifragum plants by the oral or parenteral routes and the resulting nephrotoxicity was assessed from the increases in the concentrations of creatinine and urea in the serum. Following single intraruminal or intraperitoneal doses of extracts derived from 30 g N. ossifragum (wet weight) per kg live weight (kg lw), serum creatinine concentrations increased from about 100 mol/L to between 260 and 510 mol/L. The serum urea concentrations increased from about 5–8 mmol/L to between 11 and 66 mmol/L in individual sheep. Daily intraruminal administration of 5–30 g/kg lw to three sheep over a 10- or 15-day period increased creatinine concentrations from 100 mol/L to 300–760 mol/L, and urea concentrations from 5–8 mmol/L to 35 mmol/L. A single intraperitoneal challenge dose of 30 g/kg lw, delivered 7 or 12 days after the final intraruminal dose, did not lead to increased serum creatinine or urea concentrations, indicating that oral treatment had apparently resulted in an increased tolerance to the nephrotoxic principle(s) in N. ossifragum.     

Serum Fructosamine Concentrations in Dogs with Hypothyroidism

Serum fructosamine concentrations were measured in 11 untreated hypothyroid dogs with normal serum glucose and serum protein concentrations. The fructosamine level ranged between 276 and 441 mol/L (median 376 mol/L; reference range 207–340 mol/L). Nine of the 11 dogs had fructosamine levels above the reference range. The fructosamine levels decreased significantly during treatment with levothyroxine. It is suggested that serum fructosamine concentrations may be high in hypothyroid dogs because of decelerated protein turnover, independent of the blood glucose concentration.     

Efficacy of Chlorhexidine against Some Strains of Cultured and Clinically Isolated Microorganisms

The efficacy of chlorhexidine digluconate was determined against some strains of collected and clinically isolated bacteria and fungi. The efficacy was evaluated either by calculating a minimum inhibitory concentration (MIC) or by efficacy trials according to the guidelines of the European Committee for Standardization. The MIC values of chlorhexidine for Staphylococcus aureus, Microsporum gypseum, Microsporum canis and Trichophyton mentagrophytes were 0.625 g/ml, 12.5 g/ml, 50 g/ml and 6.25 g/ml, respectively. The in vitro efficacy of chlorhexidine was higher against ATCC strains of S. aureus and P. aeruginosa (0.5 mg/ml for 5 min and 0.5 mg/ml for 10 min, respectively) than against clinical isolates (0.5 mg/ml for 15 min and 1 mg/ml for 10 min, respectively). The antiseptic activity of aqueous solutions of chlorhexidine against spores of Bacillus subtilis, Bacillis sfericus and Clostridium perfringens required longer contact times than against the vegetative forms. Nevertheless, 5 mg/ml of chlorhexidine in water–ethanol 20:80 v/v was totally effective against the vegetative forms or spores of these microorganisms.     

Clinical Value of Fructosamine Measurements in Non-healthy Dogs

Ninety-three unhealthy dogs (including some with diabetes mellitus or insulinoma) of different ages, sex and breeds were divided into 10 groups according to their pathology. Serum fructosamine concentrations were determined using a commercial colorimetric nitroblue tetrazolium method. Diabetic dogs had the highest fructosamine concentrations (454.85±149.34 mol/L). Dogs with insulinoma had significantly lower fructosamine concentrations (202.80±31.22 mol/L), similar to those with leishmaniosis (202.83±99.83 mol/L). Fructosamine concentrations in non-healthy dogs, except those with diabetes mellitus, insulinoma or leishmaniosis, were within the reference limits previously reported.     

Cholinergic reactivity of the bovine fetal ruminal wall in vitro

Strips of rumen wall from bovine fetuses were incubated in an organ bath with acetylcholine only (0.16 to 5.12 g/ml) or in the presence of neostigmine (0.20 g/ml) or atropine (0.05g/ml). The highest reactivity was observed in the period of 4.0–5.9 months of fetal age. This reactivity could be associated with the starting point of rumen papillary development.     

Feed intake and rumen motility in dwarf goats. Effects of some α-adrenergic agonists,prostaglandins and posterior pituitary hormones

The purpose of the present investigation was to test the hypothesis that drug-induced changes in rumen contractions influence feed intake in dwarf goats. Intravenous (i.v.) administration of clonidine (1 g kg^-1 min^-1 for 10 min), xylazine (1 g kg^-1 min^-1 for 10 min), and PGF-2 (10 g kg^-1 min^-1 for 15 min) caused bradycardia and inhibition of rumen contractions. However, no appetite-stimulating effect of these drugs was observed. Other clinical changes induced by the ₂-adrenergic agonists included slight sedation and a decrease in body temperature; all clinical effects of clonidine and xylazine were partly antagonized by tolazoline pretreatment (10 g kg^-1 min^-1 for 30 min). These results suggest that the CNS control of feeding differs in ruminants and monogastric species.In dwarf goats fasted for 2 h, i.v. administration of oxytocin (0.01 IU kg^-1 min^-1 for 15 min), vasopressin (0.01 IU kg^-1 min^-1 for 15 min), octapressin (0.003 IU kg^-1 min^-1 for 15 min) or PGE (0.8 g kg^-1 min^-1 for 15 min) did not change feeding behaviour during the two observation periods (0–30 min and 180–210 min after drug infusion, respectively). In previous studies, similar doses of these drugs induced changes in heart rate and inhibition of rumen contraction in goats. These findings demonstrate that drug-induced changes in forestomach contractions do not simply cause changes in feeding behaviour. The i.v. infusion of the PGF₂ analogues etiproston (10 g kg^-1 min^-1 for 15 min), luprostiol (30 g kg^-1 min^-1 for 15 min), cloprostenol (1 g kg^-1 min^-1 for 15 min) and tiaprost (1 g kg^-1 min^-1 for 15 min) induced hypophagic effects and stimulated intestinal propulsion.     

Evaluation of Synchronization of Oestrus Based on Gonadotrophin-releasing Hormone and Its Potential Use for Fixed-Time Breeding in Tuli Beef Cows

The objective of the experiment was to compare the reproductive post-partum performance of beef cows synchronized for oestrus using prostaglandin F₂ (PGF₂) alone or with a gonadotrophin-releasing hormone (GnRH)-based drug. Fifty-five post-partum lactating Tuli cows were randomly allocated to three groups. Two groups were synchronized using either two injections of PGF₂ (500 g Prosolvin per injection) given 11 days apart (group 1), or GnRH (12.5 g Receptal per injection) followed 6 days later by an injection of 500 g PGF₂ (group 2). The cows were bred by artificial insemination 12 h after they were observed in oestrus. Group 3 was synchronized as for group 2, but a second injection of GnRH was given 54 h after the PGF₂ injection, at which time the cows were bred by artificial insemination (AI) without detection of oestrus. Blood samples were taken from the cows in group 3 and analysed for progesterone concentration to establish which cows were cycling and in oestrus before and at the time of breeding. Detection of oestrus and breeding by AI was done over 60 days. There were no significant differences (p>0.05) among the three groups in the first service and total conception rates. The percentage of cows in oestrus within 10 days of the synchronization treatment was not significantly different (p>0.05) between groups 1 and 2. The progesterone concentrations in the cows in group 3 showed that only those that were cycling at the start of the experiment responded to the synchronization treatment and conceived after fixed-time breeding. These results suggest that combinations of PGF₂ and GnRH may be of value in synchronizing oestrus and controlling breeding in Tuli cows. However, the benefit might be greater if only cows that are known to be cycling are bred in this way.     

Concentrations of C-reactive Protein in Normal Monkeys (Macaca irus) and in Monkeys Inoculated with Bordetella bronchiseptica R-5 and Measles Virus

The concentrations of C-reactive protein (CRP) in serum from normal crab-eating monkeys (Macaca irus) were measured by means of a monkey-specific turbidimetric immunoassay (TIA), and the changes in the serum CRP concentrations in crab-eating monkeys inoculated with Bordetella bronchiseptica R-5 and measles virus (Ichinose or NK 3 strain) were also examined. The CRP concentrations in sera from 54 normal crab-eating monkeys ranged from 0 to 8.3 g/ml (mean 2.2±1.9). No significant difference was found in the CRP concentrations between males and females (p>0.05). The concentrations of CRP in the sera from four crab-eating monkeys inoculated intrabronchially with 10⁹ live B. bronchiseptica increased gradually to a peak at 2 days after inoculation. The peak concentrations of CRP were from 102.4 to 313.2 g/ml, 54–96 times the preinoculative values of 1.9–5.6 g/ml. When the same four crab-eating monkeys were inoculated intrabronchially with measles virus 34 days after inoculation of B. bronchiseptica, the serum CRP concentrations did not increase. Monitoring of CRP is useful for assessing monkeys with acute B. bronchiseptica infection and will probably be of value in the diagnosis of other bacterial infections.     

Pharmacokinetics and dosing regimen of aminosidine in the dog

The kinetic behaviour of the aminoglycoside aminosidine, given at 15 mg/kg intravenously, intramuscularly and subcutaneously, was studied in 5 dogs to determine the appropriate dosage schedule. The pharmacokinetic behaviour of aminosidine in dogs was similar to that in other species, except that it was eliminated more slowly (=0.007±0.0003 min^-1). Intramuscular and subcutaneous administration produced peak serum concentrations (C _max[im]=32±6.4 g/ml; C _max[sc]=36±3.4 /ml) and times to peak concentration (T _max=60 min for both) that did not differ significantly; and neither compartmental nor non-compartmental analysis revealed any significant differences between any of the kinetic parameters obtained for these two extravenous routes of administration. Comparison of these results with previously published data suggests that aminosidine given once daily at 15 mg/kg would be as effective as, and safer than, the two or three daily administrations commonly employed in dogs.Abbreviations ALAT alanine aminotransferase - ASAT aspartate aminotransferase - AUC area under the curve - BUN blood urea nitrogen - Cl_b body clearance - C _max peak plasma concentration - CV coefficient of variation - i.m. intramuscular(ly) - i.v. intravenous(ly) - LDH lactate dehydrogenase - MIC minimal inhibitory concentration - MRT mean residence time - PAE post-antibiotic effect - PCV packed cell volume - RBC red blood cell count - s.c. subcutaneous(ly) - SD standard deviation - WBC white blood cell count - V _d(ss) distribution volume at steady state     

Quantitative capillary reversed passive latex agglutination test for C-reactive protein (CRP) in the dog

A capillary reversed passive latex agglutination test (capillary RPLA) was developed which allows quantification of serum C-reactive protein (CRP) within approximately 15 min. The logarithmic regression line (calibration curve) obtained after measuring each CRP concentration three times in twofold dilutions of a standard canine serum containing 222 g/ml of CRP was y=6.394+0.030x (r=0.995). Capillary RPLA permitted quantification of CRP in the range 6.9–222 g/ml. The coefficients of variation ranged from 10.28% to 12.40%. The recovery rates (percentage recovery) of CRP by capillary RPLA were within the range 87% to 106%. On measuring the CRP concentrations in sera from 78 dogs by capillary RPLA, single radial immunodiffusion (SRID) and enzyme-linked immunosorbent assay (ELISA), close correlations were demonstrated between SRID and capillary RPLA (y=7.250+1.109x, r=0.978), between SRID and ELISA (y=3.042+1.059x, r=0.967), and between capillary RPLA and ELISA (y=1.778+0.929x, r=0.962). Capillary RPLA may be considered useful as a routine biochemical technique for measurement of serum CRP concentration in the dog.Abbreviations CRP C-reactive protein - ELISA enzyme-linked immunosorbent assay - RPLA reversed passive latex agglutination test - SRID single radial immunodiffusion     

Central and local actions of opioids upon reticulo-ruminal motility in sheep

The effects of opioids and naloxone on cyclical forestomach motility were determined in anaesthetized and conscious sheep. To assess central or peripheral opioid actions, differential routes of administration were used. Possible dynamic effects along the innervating vagovagal reflex arc were investigated electrophysiologically at the cervical level of the vagus nerve. Further, direct influences on the smooth muscle were evaluatedin vitro on isolated longitudinal reticular strips. Additionally, the effects of some spasmogenic agents were studied for comparative purposes. In anaesthetized sheep, opioids depressed in an identical manner both the amplitude of spontaneous cyclical contractions and contractions evoked by electrical stimulation of the distal end of the cut cervical vagus. In conscious sheep, low doses of normorphine and loperamide inhibited frequency and amplitude centrally (20 g/kg and 4 g/kg via carotid artery respectively), whereas locally higher dose levels (200 g/kg and 10 g/kg via coeliac artery respectively) affected only the amplitude of cyclical contractions. Furthermore the opioid peptides Leu-, Met-enkephalin and [D-Ala²-Met⁵]-enkephalinamide preferentially depressed the amplitude of cyclical motility most efficiently if administrated via the coeliac artery. These results indicate the presence both of a central opioid action depressing frequency and amplitude and of a local opioid action depressing only the amplitude of cyclical reticulo-ruminal motility. Opioids did not alter the resting discharge of afferent tension units and similarly failed to modulate tone of reticular stripsin vitro, suggesting that the opioids act locally on the intramural neuronal plexus, possibly by diminishing the output of excitatory transmitter. Whether substance P could play a role as a vagal excitatory transmitter besides the classically implicated acetylcholine has been discussed. The central opioid mechanism is probably not situated within the gastric centres but elsewhere in the brain. Naloxone ( 100 g/kg, jugular vein) stimulated the frequency of cyclical ruminal motility only in well-defined experimental conditions, probably via a central mechanism.     

Some Pharmacokinetic Parameters of Pefloxacin in Lactating Goats

The aim of this study was to elucidate some of the pharmacokinetic parameters of pefloxacin in lactating goats (n = 5) following intravenous (i.v.) or intramuscular (i.m.) injections of 10 mg/kg bw. Serially obtained serum, milk and urine samples were collected at precise time intervals, and the drug concentrations were assayed using a microbiological assay. A two-compartment open model best described the decrease of pefloxacin concentration in the serum after intravenous administration. The maximum serum concentration (C _p ⁰ ) was 8.4±0.48 g/ml; elimination half-life (t _1/2) was 1.6±0.3 h; total body clearance (Cl_tot) was 3.6±0.3 L/kg/h; steady-state volume of distribution (V _dss) was 5.14±0.21 L/kg; and the area under the curve (AUC) was 2.78±0.22 g.ml/h. Pefloxacin was absorbed rapidly after i.m. injection with an absorption half-life (t _1/2ab) of 0.32±0.02 h. The peak serum concentration (C _max) of 0.86±0.08 g/ml was attained at 0.75 h (T _max). The absolute bioavailability after i.m. administration was 70.63±1.13% and the serum protein-bound fraction ranged from 7.2% to 14.3%, with an average value of 9.8±1.6%. Penetration of pefloxacin from the blood into the milk was rapid and extensive, and the pefloxacin concentration in milk exceeded that in serum from 1 h after administration. The drug was detected in milk and urine for 10 and 72 h, respectively; no samples were taken after 72 h.     

The Pharmacokinetics of a Long-acting Oxytetracycline Formulation in Healthy Dogs and in Dogs Infected with Ehrlichia canis

The pharmacokinetic properties of oxytetracycline were studied following a single injection of a long-acting formulation (20 mg/kg body weight) into the semimembranosus muscle of healthy dogs and of dogs that had been experimentally infected with Ehrlichia canis. The disposition curves of the long-acting oxytetracycline formulation before and after infection were best described by a bi-exponential decline after a first-order absorption. The mean maximum serum concentration (C _max) following infection was significantly lower and the time taken to attain this concentration (t _max) was significantly shorter than that in the healthy dogs. The mean apparent elimination half-life (t _1/2) was significantly increased following infection. The corresponding rate constant () was significantly decreased. The absorption half-life (t _1/2ab) was significantly decreased after infection. The volume of distribution at steady state (V _dss) increased significantly following infection. It was concluded that the pharmacokinetic behaviour of a long-acting oxytetracycline in dogs after intramuscular administration is characterized by a two-compartment model with a slow elimination phase. This could be due to flip-flop kinetics. The febrile reaction in experimental E. canis infection affected some pharmacokinetic parameters of oxytetracycline.     

Immunological determination of faecal haemoglobin concentrations in dogs

Faecal haemoglobin (Hb) concentrations in apparently healthy experimental Beagle dogs and in dogs of various breeds kept in private households or at breeders were measured by reversed passive latex agglutination (RPLA) and enzyme-linked immunosorbent assay (ELISA) in an effort to define the physiological concentrations of faecal Hb in the dog. In 88% (53) of 60 experimental Beagle dogs (30 males and 30 females), the RPLA titres were 1:2 and 1:8 and the faecal Hb concentrations ranged from 40.0 to 431.5 (mean 184.1±92.6) g/g faeces by ELISA. No significant difference was found in Hb levels or RPLA titres between males and females. Seven dogs (12%) had significantly greater RPLA titres and Hb concentrations by ELISA than the remaining dogs. In 84% (45) of the 53 dogs kept in private households or at breeders, the RPLA titres were >1:1 to 1:8 and the faecal Hb concentrations ranged from 7.1 to 456.7 (mean 137.5±128.7) g/g faeces in ELISA. Eight of these dogs (15.1% of 53 dogs) had significantly greater RPLA titres and Hb concentrations by ELISA than the remaining dogs. There were no significant differences between the Beagles and dogs kept in private households or at breeders. In conclusion, in 98 (86.7% of 113) dogs the physiological concentrations of RPLA titres were >1:1 to 1:8 and the faecal Hb concentrations were 143.5–185.1 g/g (95% confidence level). Approximately 13.3% of apparently healthy dogs had higher faecal Hb concentrations, suggesting the presence of subclinical haemorrhages. Four dogs suffering from colorectal cancer also had high faecal Hb concentrations.     

Pharmacokinetics of Pefloxacin in Goats after Intravenous or Oral Administration

The plasma concentrations and pharmacokinetics of the fluoroquinolone antimicrobial agent pefloxacin, following the administration of a single intravenous (10 mg/kg) or oral (20 mg/kg) dose, were investigated in healthy female goats. The antimicrobial activity in plasma was measured at predetermined times after drug administration by an agar well diffusion microbiological assay, using Escherichia coli (ATCC 25922) as the test organism. Concentrations of the drug 0.25 g/ml were maintained in plasma for up to 6 and 10 h after intravenous (IV) or oral administration of pefloxacin, respectively. The concentration–time data for pefloxacin in plasma after IV or oral administration conformed to two- and one-compartment open models, respectively. Plasma pefloxacin concentrations decreased rapidly during the initial phase after IV injection, with a distribution half-life (t _1/2 ) of 0.10±0.01 h. The terminal phase had a half-life (t _1/2 ) of 1.12±0.21 h. The volume of distribution at steady state (V _dss), mean residence time (MRT) and total systemic clearance (Cl_B) of pefloxacin were 1.08±0.09 L/kg, 1.39±0.23 h and 821±88 (ml/h)/kg, respectively. Following oral administration of pefloxacin, the maximum concentration in the plasma (C _max) was 2.22±0.48 g/ml and the interval from administration until maximum concentration (t _max) was 2.3±0.7 h. The absorption half-life (t _{1/2 ka}), mean absorption time (MAT) and elimination half-life of pefloxacin were 0.82±0.40, 4.2±1.0 and 2.91±0.50 h, respectively. The oral bioavailability of pefloxacin was 42%±5.8%. On the basis of the pharmacokinetic data, a dosage regimen of 20 mg/kg, IV at 8 h intervals or orally twice daily, is suggested for treating infections caused by drug-sensitive pathogens in goats.     

Plasma,Urinary and Biliary Residues in Cattle Following Intramuscular Injection of Nortestosterone Laurate

The synthetic androgen 19-nortestosterone (-NT) has been used illegally as a growth promoter in cattle production in the European Union. Elimination of -NT and its metabolites in plasma, urine and bile was studied in three cattle with cannulated gallbladders following intramuscular injection at a single site of 500 mg of the laurate ester (NTL) containing 300.5 mg -NT. Using enzyme immunoassay quantification, plasma Cmax of free -NT was 0.5±0.15 g/L (mean±SEM). Concentrations of free -NT in plasma were consistently greater than the assay limit of quantification (0.12 g/L) for 32.7±13.42 days. Mean residence time for free -NT in plasma was 68.5±20.75 days. Following sample preparation by immunoaffinity chromatography, high-resolution GC-MS was used to quantify -NT and -NT in urine and bile. -NT was detected irregularly in urine from two of the three animals post injection. The principal metabolite present in the urine, -NT, was detected for 160.3±22.67 days post injection. Cmax for -NT in urine was 13.7±5.14 g/L. Mean urinary AUC0–183 days for -NT was 845.7±400.90 (g h)/L.In bile, -NT was the only metabolite detected for 174.3±8.67 days post treatment. Cmax for -NT in bile was 40.8±12.70 g/L and mean biliary AUC0–183 days for -NT was 1982.6±373.81 (g h)/L. Concentrations of -NT in bile samples were greater than those in urine samples taken at the same time. The mean ratio of biliary:urinary AUC0–183 days was 3.0±0.72. It is concluded that bile is a superior fluid for detection of -NT following injection of NTL, owing to the longer period during which residues may be detected after administration.     

Disposition kinetics and distribution of demeclocycline in various biological fluids in female goats

A pharmacokinetic study of demeclocycline was carried out following intravenous administration at 5 mg/kg body weight in lactating goats. Demeclocycline appeared within 5 min in plasma, interstitial fluid (isf) and urine, while it appeared at 1 h in milk. Peak concentrations of 21.70±4.06, 2.67±0.23, 5.65±0.45 and 82.23±10.06 g/ml were attained at 5 min and at 6, 8 and 8 h in plasma, isf, milk and urine respectively. A potentially therapeutic concentration of 0.5 g/ml was maintained from 5 min–36 h, 30 min–30 h, 1–36 h and 5 min–48 h in plasma, isf, milk and urine respectively. The drug was detectable in all the above biological fluids for at least 48 h. A low distribution half life (t_1/2) of 0.44±0.04 h and a high elimination half life (t_1/2) of 19.24±1.22 h denote rapid distribution but very slow elimination of the drug in goats. A high tissue plasma concentration ratio [K₁₂:(K_2I–)] of 5.12±0.97 during the elimination phase and a Vd_area of 1.59±0.18 L/kg indicate uniform distribution of demeclocycline in the tissues and body fluids of goats. The dosage regimen for maintaining minimum plasma concentration (C min = MIC) of 0.5, 1.0 and 1.5 g/ml at selected dosage intervals of 12 and 24 h was also calculated.