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The problem of no residues is elucidated and discussed under pharmacokinetic aspects. An equation with due consideration confidence by which to calculate the absence of residues in drugs is given under the assumption that elimination of such residues should follow the concepts of the monocompartment model. The time is calculated by which all residues of sulphamerazine have disappeared, following application of Mebacid 200 and Mebacid tablets to farm animals.

Pharmacokinetic data of sulphamerazine were recorded from eight heads each of calf, adult cattle, horse, and sheep, following intravenous application of Mebacid 200, and mathematical implications were discussed. Exponential excretion was recorded from all species, according to the following equation: c = B x e-k2 x t The most favourable pharmacokinetic parameters were recorded from calf.

The pharmacokinetic properties of sulphaperine-sodium, Mebacid 200, and sulphadimidine-sodium were experimentally established from fowl and mathematically objectivated. The highest half-life for elimination, coupled with low protein fixation, was recorded from sulphadimidine, by comparison of the above three sulphonamides. These data were used in dosage calculations for clinical testing.

The formula proposed by RITSCHEL (1973) for calculation of rates of resorption is explained and modified for use of the monocompartment model. Resorption rates were calculated for cattle, calf, horse, and sheep, with reference being made to the example of Mebacid tablets. The most favourable rate of resorption was established for calf.

The pharmacokinetic properties of sulphamerazine, following oral application of granulated Mebacid to cattle, calf, and sheep, were compared with results obtained from the use of Mebacid tablets. Elimination half-life was higher in cattle, calf, and sheep, following oral application of Mebacid tablets. Different pharmacokinetic properties of sulphamerazine were found to exist between the two modes of preparation. Sulphonamide was eliminated more rapidly by cattle, calf, and sheep, when granulated Mebacid was used. When granulate is used, higher sulphamerazine doses have to be applied to calf and sheep to obtain the sulphonamide levels required for effective therapy. No intolerance was recorded from the above species, following oral application of granulated Mebacid.

The mathematical foundations underlying pharmacokinetic testing and acceptance of medicaments for domestic mammals are expounded and discussed, with reference being made to examples of intramuscular, subcutaneous, and oral application of Mebacid 200 and Mebacid tablets. Elimination of sulphamerazine may be mathematically described by means of the following bi-exponential function: c = B x e-k2 x t -- A x e-k1 x t The concepts of the mono-compartmental model "Extravasal Application" can be claimed as being of basic validity. Blood levels established after intramuscular and subcutaneous application of sulphamerazine-sodium (Mebacid 200) were lower than those recorded after oral application of Mebacid tablets. The half-lives of elimination, following oral application to big animals of Mebacid tablets, were longer than those following intravenous application of comparable injection solution.

The highly variegated complex of aspects relating to dosage calculation for veterinary drugs is explained and discussed by examples of Mebacid 200 and Mebacid tablets. For domestic mammals, a dosage interval of 24 hours is desirable for reasons of economy. Therefore, due allowance must be made, by means of unilateral confidence, of the most unfavourable case of high protein fixation, low half-life for elimination, and high coefficient of distribution. The following equation, proposed by DETTLI and SPRING (1966) was used for dosage calculation: AD = c . delta' . ek2 . t or ED = c . delta' . (ek2 . t -1) The dosage will now be in a twelve-hour rhythm, because of the low half-life for elimination of sulphamerazine-Na. A pharmacokinetically founded dosage interval of 24 hours will be feasible only by oral application of Mebacid tablets. The difference between the calculated initial and maintenance doses was found to be negligible.