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The authors report on the current status of work on residues of veterinary medicinal products and, in particular, antimicrobial residues in foods of animal origin. This review focuses on residues of veterinary antimicrobials, antimicrobials used in livestock production, the concept of residues, and antimicrobial residues in foods of animal origin. Only one antimicrobial substance has been approved in the West African Economic and Monetary Union, compared with 16 substances in Benin and 56 in the European Union. The issue of antimicrobial residues in foods of animal origin has rarely been a serious concern in developing countries, in contrast to the situation in Europe. However, while the prevalence of veterinary drug residues in foods of animal origin is less than 1% in Europe, in some African countries it can be as high as 94%. Antimicrobial residues in foods of animal origin can cause allergies, cancer, alterations in the intestinal flora, bacterial resistance and the inhibition of fermentation in the dairy industry. The harmonisation of regulations in Africa could reduce the circulation of prohibited antimicrobials and lead to the implementation of a plan for the control and surveillance of residues from veterinary medicinal products in foods of animal origin.

In order to achieve the harmonization of validation strategies, the interpretation of several validation criteria is proposed. Furthermore, a simple and visual decision tool to assess the validity of an analytical procedure is described: the accuracy profile based on the estimation of the total error of the measurements. This profile build with beta-expectation tolerance intervals can also compute with efficiency the uncertainty related to the results of a laboratory, which is an essential parameter for the accreditation of laboratories under ISO 17025.

Pharmacokinetic variables of skeletal muscle creatine kinase were determined in sheep after intravenous and intramuscular administration of the semipurified enzyme. Catheters implanted in the jugular vein were used for both intravenous injections and blood withdrawals. Blood sample collection by vacutainer and hemolysis may in fact have considerable effects on the measurement of creatine kinase activity in plasma. The change in the enzyme activity versus time in the plasma, after intravenous administration (123 +/- 38 U/kg) of creatine kinase, was fitted by a biexponential model. The mean volume of the central compartment (45 +/- 5 mL/kg) was approximately equal to the plasma volume. Plasma half-life and plasma clearance of creatine kinase were 3.7 +/- 1.7 h and 23 +/- 8 mL.kg-1.h-1, respectively. Mean plasma bioavailability of creatine kinase after intramuscular administration (357 +/- 36 U/kg) in both the loins and the gluteal mass was 42%. Maximal plasma activity was observed 4 and 5 h after injection and the half-life of the terminal phase was 7.3 or 8.6 h according to the muscle. The extent of muscle damage after intramuscular administrations of 21 veterinary drug formulations (one product per animal) was estimated from the total creatine kinase activity released in plasma during the 72 h following the injection. Equivalent weights of damaged muscle ranged from 1.4 to 83.3 g according to the irritant potency of the test formulation. Results differed only moderately between the injection sites (right and left gluteal mass) in the same animal. It can be concluded from this study that, in sheep: i) the bioavailability of creatine kinase from different injection sites (gluteal mass and loins) is comparable; and ii) the intra-individual variability in the estimation of muscle damage is moderate. Once validated, this non-invasive approach for local tolerance studies could be of value in assessing and comparing the irritant potency of veterinary drugs and in reducing the number of animals required.

Pharmacodynamics studies consider three main parameters: the size of the bacterial population, the concentration of the antibiotic and the duration of its action. The pharmacodynamic characteristics of colistin were studied in vitro with Escherichia coli. The bacterial kinetics were fitted using differential equations. The mathematical model gave qualitative and quantitative information about the characteristics of the antibiotic-bacteria association. Above all, when linked to a pharmacokinetic model, the model permitted the prediction of the drug's efficiency. Simulations of various dosage levels in which the administration route, dose size, or interval between doses varied, permitted a more rational optimization than a prediction of efficacy based on the time taken to achieve antibiotic plasmatic concentrations above the minimal inhibitory concentration. Pharmacokinetic/pharmacodynamic modeling seems to be an interesting possibility for determining antibiotic dosing levels during the preclinical phase.

The modelling of in vitro growth curves of Staphylococcus aureus ATCC 6538P at different pHs, of spiramycin killing curves and of the dose-effect relationship was performed. The growth curve was characterised by a Volterra-Kostitzin differential model, the main parameters of which were the bacterial growth rate constant of 0.95 +/- 0.13 h-1 and a lag-time of 0.74 +/- 0.36 h. The Zhi model used for bactericidal kinetics showed the same bacterial killing rate constant from a minimum concentration characteristic of "time-dependent" antibiotics. This differential model incorporated with pharmacokinetic models could lead to a rationale for proper dosage regimens.

Pharmacokinetic characteristics of an extemporaneous form of colistin sulfate in young calves were studied for a dosage of 25,000 IU.kg-1. The intravenous route (IV) is characterized by a 3-compartment model whose main parameters are: volume of distribution (1.02 l.kg), body clearance (0.15 l.h-1 kg-1) and mean residence time (3.87 h). By intramuscular route (IM), a mean serum peak of 37 IU.ml-1 was reached at a mean time of 0.5 h. The mean half-time of terminal phase (6.47 h) does not differ significantly from that of the intramuscular route (4.52 h). Absolute bioavailability calculated based on 4 calves was 109 +/- 28%. Repeated IM administrations seem to be adapted to maintain a bactericidal activity and to reduce risks of toxicity and neurological disorders (25,000 IU.kg-1) every 12 h over 3d.