The distribution of oxytetracycline in the tissues of Swine following a single oral dose

A single oral dose of oxytetracycline hydrochloride (50 mg/kg) produced detectable residues in the following tissues; adrenal, bile, fat, heart, kidney (cortex), kidney (medulla), liver, lung, lymph node (mesenteric), muscle, serum, spleen, thyroid and urine. The highest residue levels were observed in the urine (441 μg/mL) at three hours after administration and they were still present at 48 hours. Maximum serum levels were observed at two hours after administration. Bile samples were positive for inhibitors in all animals sampled. Drug residues were not detected in spleen, thyroid, lymph node, adrenals and heart at 48 hours.

Drug levels in important edible tissues were expressed as a percentage of drug levels in two tissues with high drug concentrations — urine and kidney cortex. The percentages were highly variable when compared with urine and much less variable when compared to kidney cortex.

Kidney cortex appears to be an excellent tissue for drug residue monitoring.

     

Distribution of neomycin in bull calves after intramuscular injection

Neomycin sulfate was injected intramuscularly in calves. Blood and tissue samples were taken at zero, one, two, four, six, eight and 24 hours after administration. The tissues with high levels (greater than 10 μg/g) of drug at the one hour period were kidney cortex and medulla, urine, blood serum and the injection site. By 24 hours after administration only the kidney cortex and urine had high levels of neomycin. The drug could not be detected in any brain tissues and very small amounts (less than 1 μg/g) were present in the bile, thymus and vitreous humor. Levels greater than 5 μg/g were present in lung tissues for less than four hours but were greater than 2 μg/g for more than 24 hours.

The mean level in the injection site was greater than 700 μg/g at one hour but only trace amounts were found at 24 hours.

On the basis of the tissue drug concentration intramuscularly administered neomycin was suggested as therapeutically useful for respiratory and urinary tract infections caused by susceptible bacteria.

     

Disposition kinetics and urinary excretion of ciprofloxacin in goats following single intravenous administration

We evaluated the pharmacokinetics of ciprofloxacin in serum (n = 6) and urine (n = 4) in goats following a single intravenous administration of 4 mg/kg body weight. The serum concentration-time curves of ciprofloxacin were best fitted by a two-compartment open model. The drug was detected in goat serum up to 12 h. The elimination rate constant (β) and elimination half-life (t_1/2β) were 0.446 ± 0.04 h^-1 and 1.630 ± 0.17 h, respectively. The apparent volume of distribution at steady state (Vd_ss) was 2.012 ± 0.37 l/kg and the total body clearance (Cl_B) was 16.27 ± 1.87 ml/min/kg. Urinary recovery of ciprofloxacin was 29.70% ± 10.34% of the administered dose within 36 h post administration. In vitro serum protein binding was 41% ± 13.10%. Thus, a single daily intravenous dose of 4 mg/kg is sufficient to maintain effective levels in serum and for 36 h in urine, allowing treatment of systemic, Gram-negative bacterial infections and urinary tract infections by most pathogens.     

Subcutaneous pharmacokinetics and dosage regimen of cefotaxime in buffalo calves (Bubalus bubalis)

The pharmacokinetics and dosage regimen of cefotaxime following its single subcutaneous administration (10 mg/kg) were investigated in buffalo calves. Plasma and urine samples were collected over 10 and 24 h post administration, respectively. Cefotaxime in plasma and urine was estimated by microbiological assay technique using E. coli as test organism. The pharmacokinetic profiles fitted one-compartment open model. The peak plasma levels of cefotaxime were 6.48 ± 0.52 µg/ml at 30 min and the drug was detected upto 10 h. The absorption half-life and elimination half-life were 0.173 ± 0.033 h and 1.77 ± 0.02 h, respectively. The apparent volume of distribution and total body clearance were 1.17 ± 0.10 l/kg and 0.45 ± 0.03 l/kg/h, respectively. The urinary excretion of cefotaxime in 24 h, was 5.36 ± 1.19 percent of total administrated dose. A satisfactory subcutaneous dosage regimen for cefotaxime in buffalo calves would be 13 mg/kg repeated at 12 h intervals.     

Peptococcus (S. Micrococcus) indolicus. The demonstration of two varieties of hemolysin forming strains.

On the basis of biochemical and serological criteria 2 hemolysin forming varieties of peptococci were identified as Peptococcus indolicus.Of a total of 16 hemolytic strains examined 9 originated from the vagina of clinically healthy cows, 4 from mastitis secretions from dry cows, 2 from the interdigital skin of clinically healthy sows, and 1 from a subcutaneous abscess in a pig.Two strains were designated a-hemolytic and 14 β-hemolytic.On blood agar plates colonies of the α-hemolytic variety were surrounded by narrow zones of almost complete hemolysis, while colonies of the β-hemolytic variety were surrounded by broad zones of incomplete hemolysis. The hemolysins were termed α- and β-hemolysin, respectively.The β-hemolysin, but not the α-hemolysin, could be demonstrated in cultures grown in liquid media. The β-hemolysin was found to be filtrable, relatively thermoresistant, and non-dermonecrotic.By gel diffusion analyses the 2 α-hemolytic strains were referred to Serotype C. Ten of the β-hemolytic strains belonged to Serotype C, 2 to Type B, 1 to Type D, and 1 to Type E.     

Clinical pharmacokinetics of norfloxacin-glycine acetate after intravenous and oral administration in pigs

The pharmacokinetics and dosage regimen of norfloxacin-glycine acetate (NFLXGA) was investigated in pigs after a single intravenous (i.v.) or oral (p.o.) administration at a dosage of 7.2 mg/kg body weight. After both i.v. and p.o. administration, plasma drug concentrations were best fitted to an open two-compartment model with a rapid distribution phase. After i.v. administration of NFLXGA, the distribution (t_1/2α) and elimination half-life (t_1/2β) were 0.36 ± 0.07 h and 7.42 ± 3.55 h, respectively. The volume of distribution of NFLXGA at steady state (Vd_ss) was 4.66 ± 1.39 l/kg. After p.o. administration of NFLXGA, the maximal absorption concentration (C_max) was 0.43 ± 0.06 µg/ml at 1.36 ± 0.39 h (T_max). The mean absorption (t_1/2ka) and elimination half-life (t_1/2β) of NFLXGA were 0.78 ± 0.27 h and 7.13 ± 1.41 h, respectively. The mean systemic bioavailability (F) after p.o. administration was 31.10 ± 15.16%. We suggest that the optimal dosage calculated from the pharmacokinetic parameters is 5.01 mg/kg per day i.v. or 16.12 mg/kg per day p.o.     

Antimicrobial residues in milk. Comparison of different agar diffusion methods

Different agar diffusion methods were compared in order to find a sensitive method for the detection of various antimicrobial residues in milk. A total of 588 producer milk samples were analyzed using subsets of the most sensitive methods.With the IDF method, 2 positive cases (0.34 %) appeared among the producer milk samples, with the Thermocult method 13 positive cases (2.21 %) and with the Test agar pH 8 method with trimethoprim and glucose 4 positive cases (0.68 %). A combination of the IDF method and the Test agar pH 8 method resulted in 6 positive cases (1.02 %) and a combination of the Thermocult method and the Test agar pH 8 method in 17 positive cases (2.89 %). With penicillinase 41 % of the positive cases were identified as β-lactam antibiotics and with p-aminobenzoic acid 18 % of the positive cases were identified as sulphonamides. 41 % of the positive cases remained unexplained.The best combination for the detection of antimicrobial agents in milk seems to be that of the Thermocult method and the Test agar pH 8 method with trimethoprim and glucose.     

Drug residues in food animals. I. Plasma and tissue kinetics of chloramphenicol in young cross-bred swine

Eighteen non-fasted, 12–16 week old pigs weighing between 20 and 40 kg were dosed with chloramphenicol intravenously at a dose rate of 22 mg/kg body weight. The pharmacokinetics of chloramphenicol were determined in blood plasma and sixteen selected organs and body fluids. The elimination half-life in plasma was estimated to be 2.66pL1.06 h and volume of distribution was 1.39pL0.32 I/kg. The body clearance of chloramphenicol was estimated to be 6.64pL1.52 ml/kg/min. The elimination half-life in tissue was found to range from 1.25 h in kidney to 5.89 h in fat. Most major organs ranged from 2.0 to 5.0 h. Significant correlations were found to exist between plasma concentrations and most major organ concentrations. Chloramphenicol concentrations in muscle, spleen, lung, stomach content, and large intestine content were found to exist slightly beyond the time when concentrations were negative in plasma. However, urine levels exceeded tissue levels at the last slaughter interval. It appears that serum or urine would be a good body fluid for monitoring chloramphenicol residues in tissues, whereas stomach content might be used as an indicator for chloramphenicol treatment for many days after therapy with the drug.     

Pharmacokinetics, urinary excretion and dosage regimen of levofloxacin following a single intramuscular administration in cross bred calves

The pharmacokinetics and urinary excretion following single intramuscular administration of levofloxacin at a dose of 4 mg/kg was investigated in seven male cross bred calves. Appreciable plasma concentration of levofloxacin (0.38 ± 0.06 µg/ml) was detected at 1 min after injection and the peak plasma level of 3.07 ± 0.08 µg/ml was observed at 1 h. The drug level above MIC₉₀ in plasma was detected up to 12 h after administration. Rapid absorption of the drug was also evident by the high value of the absorption rate constant (2.14 ± 0.24 /h). The overall systemic bioavailability of levofloxacin, after intramuscular administration, was 56.6 ± 12.4%. The high value of AUC (7.66 ± 0.72 mg . h/ml) reflected the vast area of body covered by drug concentration. Extensive distribution of the drug into various body fluids and tissues was noted by the high value of Vd_area (1.02 ± 0.05 l/kg). The high ratio of AUC/MIC (76.6 ± 7.25) obtained in this study indicated excellent clinical and bacteriological efficacy of levofloxacin in calves. The elimination half-life and MRT were 3.67 ± 0.4 h and 5.57 ± 0.51 h, respectively. The total body clearance (Cl_B) was 204.9 ± 22.6 ml/kg/h. On the basis of the pharmacokinetic parameters, a suitable intramuscular dosage regimen for levofloxacin in calves would be 1.5 mg/kg repeated at 12 h intervals.     

乳酸菌发酵驼乳工艺优化及抑制α-淀粉酶和α-葡萄糖苷酶活性的研究

[目的]以实验室前期从驼乳中分离得到的乳明串珠菌、副干酪乳杆菌为对象,并通过体外实验对发酵驼乳抑制α-淀粉酶和α-葡萄糖苷酶活性以及抗氧化能力进行测定。[方法]以α-淀粉酶抑制率和α-葡萄糖苷酶抑制率为考察指标,在单因素试验的基础上,采用正交试验优化发酵驼乳的参数条件。测定在不同储藏时间下试验组乳明串珠菌、副干酪乳杆菌发酵驼乳、对照组乳明串珠菌、副干酪乳杆菌发酵牛乳和嗜热链球菌、保加利亚乳杆菌发酵驼乳pH值、酸度、活菌数、α-淀粉酶抑制率、α-葡萄糖苷酶抑制率、羟自由基和超氧阴离子自由基清除率的变化。[结果]驼乳发酵的最佳工艺条件为乳明串珠菌∶副干酪乳杆菌比例2∶3、接种量2%、发酵温度39 ℃,发酵时间24 h,此条件下测得对α-淀粉酶和α-葡萄糖苷酶的抑制率分别达到87.20%和20.85%,与未优化前相比,α-淀粉酶的抑制率提高14.10%,α-葡萄糖苷酶抑制率提高4.4%。在4 ℃储藏期间发酵驼乳α-淀粉酶抑制率在第6d时最高为90.39%,对α-葡萄糖苷酶的抑制率最高为36.32%,抑制率显著高于对照组。各组对羟自由基的清除率达到70%以上,最高为94.91%,超氧阴离子自由基清除率最高达到78.10%,整个测定过程中试验组的抗氧化活性均显著高于对照组。[结论]经乳酸菌发酵驼乳抑制α-淀粉酶和α-葡萄糖苷酶活性提高,在储藏期间抗氧化活性显著高于对照组（P<0.05）。     

Serum bile acids as an indicator of liver disease in dogs

Total serum bile acids were determined in 62 dogs with different primary or secondary liver diseases, using 3α-hydroxysteroid dehydrogenase coupled to nitrobluetetrazolium in a centrifugal analyzer. A reaction time of 4 min was sufficient, yielding a within run coefficient of variation of 7% at 6 µmol/1 and 3% at 27 µmol/1. A reference range of 0–4.4 µmol/1 2 h post prandially was observed. The sensitivity of bile acids as a liver function test was superior to that of alanine and aspartate aminotransferase, alkaline phosphatase, γ-glutamyltransferase and combinations of two of these. The bile acids test detected 36 of 39 patients with a morphological or clinical liver diagnosis. For dogs with heart failure the bile acids test was a markedly more sensitive indicator of secondary liver involvement than alanine aminotransferase or alkaline phosphatase. For secondary liver affections associated with pyometra or epilepsy medication the opposite was the case. Bile acid values in the pooled patient material was not correlated to any of the 4 enzymes measured. For cirrhosis there was positive correlation, however, with the amino transferase values.     

羊奶粉中氯霉素类药物残留液相色谱-串联质谱法的研究

[目的]研究羊奶粉中氯霉素、甲砜霉素、氟甲砜霉素残留的液相色谱-串联质谱测定方法。[方法]样品经乙腈提取,固相萃取柱净化,以甲醇水作为流动相,采用多反应监测负离子模式进行定性及内标法定量分析。[结果]氯霉素、甲砜霉素、氟甲砜霉素的相关系数均大于0.999,氯霉素检出限为0.1μg/kg,甲砜霉素和氟甲砜霉素检出限为0.2μg/kg;氯霉素加标回收率为100.9%～116.2%,甲砜霉素加标回收率为88.4%～99.6%,氟甲砜霉素加标回收率为89.6%～103.2%。[结论]该方法灵敏度高、准确性好,适于测定羊奶粉中氯霉素、甲砜霉素,氟甲砜霉素的残留量。     

Cortisol Concentrations in Well‐Regulated Dogs with Hyperadrenocorticism Treated with Trilostane

Background

There are no clear treatment guidelines for dogs with clinically well‐regulated hyperadrenocorticism in which serum cortisol concentrations before and after an ACTH stimulation test performed 3–6 hours after trilostane administration are < 2.0 μg/dL.

Objective

To determine if serum cortisol concentrations measured before (Pre1) and after (Post1) ACTH stimulation at 3–6 hours after trilostane administration are significantly lower than cortisol concentrations measured before (Pre2) and after (Post2) ACTH stimulation 9–12 hours after trilostane administration, in a specific population of dogs with clinically well‐regulated hyperadrenocorticism and Pre1 and Post1 <2 μg/dL.

Animals

Thirteen client‐owned dogs with clinically well‐regulated hyperadrenocorticism and Pre1 and Post1 serum cortisol concentrations <2.0 μg/dL 3–6 hours after trilostane administration.

Methods

Prospective study. Dogs had a second ACTH stimulation test performed 9–12 hours after trilostane administration, on the same day of the first ACTH stimulation test. Cortisol concentrations before and after ACTH stimulation were compared using a paired t‐test.

Results

Cortisol concentrations before (1.4 ± 0.3 μg/dL) and after the first stimulation (1.5 ± 0.3 μg/dL, mean ± SD) were significantly lower than cortisol concentration before the second stimulation (3.3 ± 1.6 μg/dL, P = .0012 each). Cortisol concentration before the first stimulation was also significantly lower than cortisol concentration after the second stimulation (5.3 ± 2.4 μg/dL, P = .0001).

Conclusions and clinical importance

In dogs with clinically well‐regulated, trilostane‐treated, hyperadrenocorticism, and cortisol concentrations <2 μg/dL before and after the first stimulation, a second ACTH stimulation test performed 9–12 hours after treatment can result in higher cortisol concentrations that could support continued trilostane treatment.     

Detection and characterization of Clostridium perfringens in the feces of healthy and diarrheic dogs

Clostridium perfringens has been implicated as a cause of diarrhea in dogs. The objectives of this study were to compare 2 culture methods and to evaluate a multiplex polymerase chain reaction (PCR) assay to detect C. perfringens toxin genes alpha (α), beta (β ), beta 2 (β2), epsilon (ɛ), iota (ι), and C. perfringens enterotoxin (cpe) from canine isolates. Fecal samples were collected from clinically normal non-diarrheic (ND) dogs, (n = 105) and diarrheic dogs (DD, n = 54). Clostridium perfringens was isolated by directly inoculating stool onto 5% sheep blood agar (SBA) and enrichment in brain-heart infusion (BHI) broth, followed by inoculation onto SBA. Isolates were tested by multiplex PCR for the presence of α, β, β2, ɛ, ι, and cpe genes. C. perfringens was isolated from 84% of ND samples using direct culture and from 87.6% with enrichment (P = 0.79). In the DD group, corresponding isolation rates were 90.7% and 93.8% (P = 0.65). All isolates possessed the α toxin gene. Beta (β), β2, ɛ, ι, and cpe toxin genes were identified in 4.5%, 1.1%, 3.4%, 1.1%, and 14.8% of ND isolates, respectively. In the DD group, β and β2 were identified in 5%, ɛ and ι were not identified, and the cpe gene was identified in 16.9% of isolates. Enrichment with BHI broth did not significantly increase the yield of C. perfringens, but it did increase the time and cost of the procedure. C. perfringens toxin genes were present in equal proportions in both the ND and DD groups (P ≤ 0.15 to 0.6). Within the parameters of this study, culture of C. perfringens and PCR for toxin genes is of limited diagnostic usefulness due to its high prevalence in normal dogs and the lack of apparent difference in the distribution of toxin genes between normal and diarrheic dogs.     

Pharmacokinetic, residue and irritation aspects of chloramphenicol sodium succinate and a chloramphenicol base formulation following intramuscular administration to ruminants

The disposition of chloramphenicol (CAP) and of its glucuronide metabolite in plasma and milk was studied following a single intramuscular injection of a chloramphenicol base formulation (Amicol Forte; product A) and of chloramphenicol sodium succinate (product B) to dairy cows. The dose applied of both formulations was equivalent to 50 mg CAP base/kg body weight. The HPLC determined CAP concentrations were microbiologically active. Product A revealed 30% higher plasma CAP peak concentrations (13.0 vs 9.0 micrograms/ml) and 36% larger areas under the plasma concentration-time curves than product B, whereas their absorption and elimination half-lives were of the same order of magnitude. In the onset phase (during 4 h p.i.) unhydrolysed CAP sodium succinate could be detected in plasma and the glucuronide fraction was 26% of the parent drug. After 25 h p.i. the glucuronide fraction equalled that of the parent drug. The maximum CAP concentration in milk was for product B equal to, and for product A 80% of, the CAP plasma concentration. In milk no chloramphenicol glucuronide metabolites could be detected. HPLC methods for detecting ultra-trace CAP concentrations in edible tissues were developed by the employment of extraction with or without a clean-up procedure. Seven days after i.m. administration of product A and B to calves, the CAP residue concentrations in the kidney, liver, and muscle were less than 2 nanogram/g tissue. Traces of CAP residues could be still found at the injection site and in the urine. Chloramphenicol sodium succinate (product B) caused extensive tissue irritation at the injection site, while in the case of product A the irritation was limited.(ABSTRACT TRUNCATED AT 250 WORDS)     

A method of extraction in the detection of residual inhibiting substances in the tissues of pigs and calves after unavoidable slaughter

Differences were studied in detecting residues of inhibitory substances in tissue samples of pigs and calves after emergency slaughter. Samples of liver, heart, kidney and muscle of 30 pigs and 16 calves were examined. Solid samples of organ tissues placed on an agar medium and extracts of the solid samples placed into agar pits were used for detection. Samples were parallelly subjected to the microbiologic diffusion method, using the S. aureus CCM 2022 and B. subtilis CCM 1999 microorganisms. The method of obtaining the extracts from solid samples of the organs was proposed and tested at our own workplace. The presence of inhibitory substances was displayed by the formation of inhibition zones. Results of the positive samples in calves (7 samples) and in pigs (3 samples) point out explicitly to the fact that the extracts of the tissue samples display positively larger inhibition zones in comparison with the solid samples. B. subtilis was demonstrated to be more sensitive than S. aureus, comparing the used microorganisms.     

Effect of ingesta on systemic availability of chloramphenicol from two oral preparations in cats

On five separate occasions, five adult cats were dosed orally with 100 mg chloramphenicol tablets or chloramphenicol palmitate suspension. Each preparation was given once when the cats were fasted and once when fed ad lib. In addition, fasted cats were given the tablet preparation on one occasion with 10 ml water orally immediately afterwards. Chloramphenicol concentrations were determined at intervals after dosing, and all urine passed in 24 h after dosing was collected for chloramphenicol assay. The initial plasma antibiotic concentrations were lower with chloramphenicol palmitate suspension than with chloramphenicol tablets, and the bioavailability of chloramphenicol from the palmitate ester was especially poor in starved cats. Chloramphenicol palmitate may thus be undesirable for antimicrobial therapy in inappetent cats. Food and fluid did not appear to influence the availability of chloramphenicol from the tablet preparation, although effects on plasma drug concentrations within 1.5 h of dosing would have been missed in this study. A relatively large proportion of an oral dose of chloramphenicol is excreted unchanged in feline urine. Because of the potential toxicity of the drug, chloramphenicol dose rates should be restricted in cats with renal insufficiency or another antibiotic used.     

Use of malathion against ectoparasites on lactating cows

The clinical effect, residues in milk and toxicological properties of a non-commercial formulation of malathion used as an ectoparasitic agent on cattle were investigated. The results show that the malathion preparation has a desired clinical effect. The maximum concentration of malathion in milk after topical application of 5 g malathion was 0.054 μg/ml 4–6 h post-treatment, and declined to 0.005 and 0.002 μg/ml 24 and 48 h post-treatment, respectively. Totally 0.006–0.03 % of the applied dose was excreted in the milk. No toxic effect, measured as inhibition of the cholinesterases in erythrocytes and plasma, could be detected after therapeutic use of malathion.The pharmacokinetic evaluation after 2.5 g intravenous administration of malathion, indicated that the kinetics could probably be described by a multicompartment model.     

Ultrasonographic evaluation of renal dimension and resistive index in clinically healthy Korean domestic short-hair cats

Renal length, height, width, resistive index (RI), size of cortex, and medulla were determined by renal ultrasonography in 50 healthy Korean domestic short-hair cats. In the sagittal plane, the renal length was 3.83 ± 0.51 cm (mean ± SD) in the left kidney and 3.96 ± 0.48 cm in the right kidney, whereas the renal height was 2.42 ± 0.27 cm in the left kidney and 2.36 ± 0.28 cm in the right kidney. In the transverse plane, the renal height was 2.42 ± 0.28 cm in the left kidney and 2.38 ± 0.27 cm in the right kidney, whereas the renal width was: 2.65 ± 0.35 cm in the left kidney and 2.63 ± 0.31 cm in the right kidney. In the dorsal plane, the renal length was 3.84 ± 0.53 cm in the left kidney and 3.97 ± 0.54 cm in the right kidney, whereas the renal width was 2.65 ± 0.34 cm in the left kidney and 2.66 ± 0.33 cm in the right kidney. There were no significant differences (p > 0.05) among the same structure sizes measured in different planes. In the sagittal plane, the size of the renal cortex was 0.47 ± 0.08 cm in the left kidney and 0.47 ± 0.08 cm in the right kidney, whereas of the size of the renal medulla was 0.55 ± 0.30 cm in the left kidney and 0.50 ± 0.07 cm in the right kidney. RI evaluated by pulsed wave Doppler sonography was 0.52 ± 0.05 in the left kidney and 0.55 ± 0.05 in the right kidney. The actual renal dimensions determined by gross examination were not statistically different from those determined by ultrasonography. Furthermore the renal dimensions and RI were statistically correlated to the body weight of cats.     

Bioavailability,pharmacokinetics and residues of chloramphenicol in the chicken*

Anadón, A., Bringas, P., Martinez-Larrañaga, M.R., Diaz, M.J. Bioavailability, pharmacokinetics and residues of chloramphenicol in the chicken. J. vet. Pharmacol Therap. 17 , 52–58. The pharmacokinetic properties of chloramphenicol were determined in broiler chickens after two sinSle oral doses (30 and 50 mg/kS body weight) and after a single intravenous (i.v.) dose (30 mg/kg body weight). After oral and i.v. administration, the plasma concentration-time graph was characteristic of a two-compartment open model. After oral administration (30 and 50 mg/kg). chloramphenicol was absorbed rapidly (time to maximal concentration of 0.72 or 0.60 h) and eliminated with a mean half-life (t_½β) of 6.8 7 or 7.41 h, respectively. The bioavailability was 29% at 30 mg/kg chloramphenicol and 38% at 50 mg/kg chloramphenicol. Concentrations greater than 5 (m̈g/ml were achieved at 15 min and persisted up to 2 or 4 h post-administration, respectively. Statistically significant differences between the two routes of administration were found for the pharmacokinetic variables, half-lives of both distribution and elimination phases (t_½αt_½β) and apparent volume of distribution [V_d(area)]. The mean t_½β of chloramphenicol and i.v. administration was 5.23 h. Chloramphenicol was extensively metabolized into dehydrochloramphenicol (DH-CAP), nitrophenylaminopropanedione (NPAP) and nitroso-chlorampheni-col (NO-CAP) derivatives. Residues of chloramphenicol (CAP) and the three metabolites DH-CAP, NPAP and NO-CAP in kidney, liver and muscle were measured in chickens that received an oral dose of 50 mg/kg once daily for 4 days. The results indicate that CAP and DH-CAP residues were cleared slowly and were at or below the detection limit of 0.005 m̈g/ml within 12 days after dosing. However, at the time of slaughter (12 days), the NPAP and NO-CAP residues were detected in the tissue.