Pharmacokinetics and tissue residues of spiramycin in cattle after intramuscular administration of multiple doses.

Pharmacokinetic variables of spiramycin and its distribution in muscle, liver, kidney, and injection sites were studied in 18 mixed-sex 1-year-old calves to assess drug withdrawal time after 2 IM administrations of 100,000 IU of spiramycin/kg of body weight at 48-hour intervals. Presence of a compound, other than spiramycin I (ie, neospiramycin), was observed in tissues used for withdrawal time determination. High concentrations observed at the injection sites decreased slowly to maximal residue limit with half-life of 109.5 hours for neospiramycin and 77.5 hours for spiramycin. At 14 days, neospiramycin concentrations were higher in kidney than in liver and half-life was different between these 2 tissues. Two methods of withdrawal time determination were used and the part of the samples without residue detected, in the calculation, was discussed. Withdrawal time of 35 days can be proposed on the basis of average daily intake determined for spiramycin, with concentration at injection sites representing 10% of the whole muscle concentration.

Pharmacokinetics of spiramycin after intravenous, intramuscular and subcutaneous administration in lactating cows.

Spiramycin is a macrolide antibiotic that is active against most of the microorganisms isolated from the milk of mastitic cows. This work investigated the disposition of spiramycin in plasma and milk after intravenous, intramuscular and subcutaneous administration. Twelve healthy cows were given a single injection of spiramycin at a dose of 30,000 IU/kg by each route. Plasma and milk were collected post injection. Spiramycin concentration in the plasma was determined by a high performance liquid chromatography method, and in the milk by a microbiological method. The mean residence time after intravenous administration was significantly longer (P less than 0.01) in the milk (20.7 +/- 2.7 h) than in plasma (4.0 +/- 1.6 h). An average milk-to-plasma ratio of 36.5 +/- 15 was calculated from the area concentration-time curves. Several pharmacokinetic parameters were examined to determine the bioequivalence of the two extravascular routes. The dose fraction adsorbed after intramuscular or subcutaneous administration was almost 100% and was bioequivalent for the extravascular routes, but the rates of absorption, the maximal concentrations and the time to obtain them differed significantly between the two routes. Spiramycin quantities excreted in milk did not differ between the two extravascular routes but the latter were not bioequivalent for maximal concentration in the milk. However, the two routes were bio-equivalent for the duration of time the milk concentration exceeded the minimal inhibitory concentration (MIC) of various pathogens causing infections in the mammary gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of automated liquid chromatographic and bioassay methods for determining spiramycin concentration in bovine plasma.

The performance of a liquid chromatographic (LC) method for spiramycin measurement in bovine plasma has been compared with that of a microbiological method. Plasma samples were obtained from cattle administered spiramycin intravenously. Comparison tests used were intraclass correlation (r1), correlation (r), and Student's paired t-test. For concentrations lower than 2.5 IU/mL, microbiological values were higher than LC values. This difference in results modified pharmacokinetic interpretation and might be explained by the presence of microbiologically active metabolites.

Chloramphenicol and oxytetracycline residues in milk and tissues from cows and bullocks treated with an injectable formulation.

A commercial formulation of chloramphenicol and oxytetracycline was administered to dairy cows and bullocks by the intramuscular route. Concentrations of drugs were determined in milk and edible tissues by high-performance liquid chromatographic and microbiological methods. The data allowed the calculation of withdrawal times for milk (4 and 17 milkings for chloramphenicol and oxytetracycline, respectively) and for tissues (35 days for chloramphenicol, more than 35 days for oxytetracycline, depending on the levels at the injection sites). Hence oxytetracycline residues were the most persistent in these types of foods, according to our dosage scheme.

Pharmacokinetics of a long-acting chloramphenicol formulation administered by intramuscular and subcutaneous routes in cattle.

The pharmacokinetic properties of a long-acting formulation of chloramphenicol were determined in six yearling cattle after a single intravenous (i.v.) administration (40 mg/kg body weight) and after two sequential subcutaneous (s.c.) or intramuscular (i.m.) administrations (90 mg/kg/48 h). The two extravascular routes were studied during a crossover trial for a bioequivalence test. After i.v. administration, the plasma concentration-time graph was characteristic of a two-compartment open model. Mean values were a half-life of 4.1 h, a volume of distribution of 0.86 l/kg and a body clearance of 0.128 l/kg/h. Plasma concentrations of chloramphenicol following i.m. and s.c. administrations increased slowly to a broad peak at 10-15 micrograms/ml between 9 and 12 h. Bioavailability was 19.1% after i.m. injection and 12.4% after s.c. administration. The extent of absorption from the two routes did not differ significantly. The rate of absorption was significantly lower after s.c. application than it was after i.m. injection. The time necessary for the plasma concentration to exceed 5 micrograms/ml was the same for the two routes. Thus, i.m. and s.c. routes are bioequivalent.

[Pharmacokinetic study of chloramphenicol in the rabbit]. / Etude pharmacocinétique du chloramphénicol chez le lapin.

Chloramphenicol was administered intravenously and orally at a dose of 50 mg/kg to ten rabbits. Pharmacokinetic parameters were calculated (rate constant of terminal phase: beta = 0.21 +/- 0.09 1/h, total body clearance: Cl = 22.7 +/- 2.1 ml/min.kg, bioavailability: F = 42.5 +/- 11.9%) and were used to discuss the proposed dosage. However, caecotrophy might occur and increase absorption of chloramphenicol.

Liquid chromatographic determination of depletion of bithionol sulfoxide and its two major metabolites in bovine milk.

A liquid chromatographic method is described for determining bithionol sulfoxide and its metabolites, bithionol and bithionol sulfone, in milk. Samples are treated with HCl to precipitate proteins and to permit extraction of bithionol sulfoxide in nonionized form. Tetrahydrofuran is added to the organic phase to facilitate extraction in diethyl ether; the dried residue is dissolved in chloroform, hexane, and sodium hydroxide and subjected to LC analysis. Residues of bithionol sulfoxide and its 2 metabolites were determined in milk of lactating cows. Holstein-Friesian dairy cows were administered a single oral dose of bithionol sulfoxide (50 mg/kg). Milk samples were analyzed with a reliable detection level of 0.025 microgram/mL for each compound. Residues of bithionol sulfoxide and bithionol were detected during 30 and 16 milkings, respectively; bithionol sulfone was never present at detectable levels.

Mutagenicity of bithionol sulfoxide and its metabolites in the salmonella/mammalian microsome test.

The mutagenic effects of bithionol sulfoxide and its two major metabolites, bithionol and bithionol sulfone, on 4 Salmonella typhimurium strains (TA97, TA98, TA100 and TA102) were investigated. Bithionol sulfoxide was found to be mutagenic to TA98 and TA100. However, mutagenicity was abolished in the presence of rat-liver S9 fractions.

High-pressure liquid chromatographic analysis of veterinary anthelmintics I: Quantitative determination of tetramisole.

High-pressure liquid chromatography was used with a 10-micron C8-type bonded silica gel column to quantitate the tetramisole in veterinary anthelmintic preparations. The chromatographic elution time was less than 10 min, and other compounds present in the products analyzed did not interefere.