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Summary 206 strains of Staph, aureus isolated from bovine mastitic milks were analysed for their susceptibility to benzylpenicillin (PEN) and dihydrostreptomycin (DHSM). On the base of MIC-determinations 43% of the strains turned out to be PEN-resistant and 33% DHSM-resistant. 97% of the PEN-resistant strains were penicillinase producers. The influence of the inoculum size on the PEN-susceptibility of the PEN-resistant group was very pronounced. On the other hand, the response of the strains to DHSM was hardly influenced by the inoculum size. The comparison of cumulative percentages of inhibition of the antibiotics used singly and combined and the analysis of the fractional inhibitory concentrations led to the conclusion of a significant synergistic effect of the combination. A synergistic effect of the combination was established also with the group of staphylococci resistant to both PEN and DHSM. The induction of penicillinase by PEN was examined on two PEN-resistant strains. The beta-lactamase production was reduced to one tenth by the concomitant influence of DHSM (PEN 100 I. U./ml, DHSM 100 mcg/ml). In an agar-diffusion assay, one tenth MIC of DHSM increased the activity of PEN 9–14 fold while PEN potentiated the efficacy of DHSM by a factor 3–7. These data are discussed with respect to the number of staphylococci that are likely to occur in the bovine udder in cases of chronic mastitis, and with regard to the concentrations of the drugs present in the mammary glands of cows treated at drying-off. The results give substantial evidence to explain the excellent therapeutic effect obtained against staphylococcal mastitis by combinations of PEN and DHSM at high dosage rates. Zusammenfassung Quantitative Erfassung der kombinierten in-vitro Aktivitaten von Benzylpenicillin und Dihydrostreptomycin auf bovine Euter-Staphylokokken unter besonderer Berucksichtigung von synergistischen Wirkungen 206 aus Milchproben isolierte Staph. aureus-Stamme wurden auf ihre Empfindlichkeit gegen Benzylpenicillin (PEN) und Dihydrostreptomycin (DHSM) untersucht. Bei einer angenommenen Grenzkonzentration von 4.1 I. E./ml resp. 37 mcg/ml wurden 43% der Stamme als PEN-resistent und 33% als DHSM-resistent klassiert. 97% der PEN-resistenten Stamme produzierten Penicillinase. Die PEN-Empfindlichkeit der PEN-resistenten Staphylokokken war stark inokulumabhangig. In viel geringerem Ausmas wurde die DHSM-Empfindlichkeit der DHSM-resistenten Stamme durch die Grose des Inokulums beeinflust. Aus dem Vergleich der kumulativen Prozentsatze der Wachstumshemmung durch die Antibiotika allein und in Kombination sowie aus einer Analyse der fraktionierten Hemmkonzentrationen (FIC) ergaben sich eindeutige Anhaltspunkte fur eine signifikante synergistische Wirkung der Kombination PEN/DHSM. Diese synergistische Wirkung kam auch bei PEN- und DHSM-resistenten Stammen zum Ausdruck. An zwei Stammen wurde die Penicillinase-Induktion durch PEN uberpruft. Es zeigte sich, das die Beta-Laktamase-Produktion durch den Einflus von DHSM auf einen Zehntel der durch PEN allein induzierten vermindert wurde. In einem Agar-Diffusionstest potenzierte eine subinhibitorische Konzentration von DHSM (ein Zehntel der minimalen Hemmkonzentration) die Wirkung von PEN um das 9 bis 14fache. Im selben Sinne (Faktor 3–7) verbesserte PEN die DHSM-Wirkung. Bei der Besprechung der genannten Versuchsresultate wird insbesondere Bezug genommen auf die Zahl der bei chronischer Mastitis im Euter zu erwartenden Staphylokokken und auf die Wirkstoffkonzentrationen nach Trockenstellbehandlung. Die Versuchsergebnisse bieten eine Erklarung fur die gute Wirkung, die eine hochdosierte PEN/DHSM-Behandlung selbst gegen durch resistente Stpahylokokken verursachte Mastitiden entfaltet. Resume Estimation quantitative de l'action combinee de benzylpenicilline et dihydrostreptomycine contre des staphylocoques isoles de mamelles de vaches avec consideration particuliere d'activites synergistiques 206 souches de Staph, aureus isolees de laits provenant de mammites bovines furent analysees quant a leur susceptibilite a la benzylpenicilline (PEN) et la dihydrostreptomycine (DHSM). Le 43% des souches fut classe resistant a PEN et 33% a DHSM sur la base de limites de concentration de 4,1 U. I./ml et 37 mcg/ml. 97% des souches resistantes a PEN produisirent de la penicillinase. La susceptibilite a PEN des staphylocoques resistants a PEN fut fortement influencee par la quantite des germes inocules. En revanche, l'activite de la DHSM fut a peine influencee par l'ampleur de l'inoculum. La comparaison des pourcentages cumulatifs de l'inhibition exercee par les antibiotiques seuls et combines et l'analyse des fractions de concentrations inhibitrices montrerent l'existence d'une synergie significative resultant de l'emploi combine des deux antibiotiques. Cette activite synergistique fut meme confirmee sur le groupe de staphylocoques a double resistance. L'induction de la penicillinase par PEN a ete examinee sur deux souches resistantes a PEN. La production de beta-lactamase resta reduite a un dixieme sous l'influence simul-tanee de DHSM (PEN 100 U. I./ml, DHSM 100 mcg/ml). Dans un essai de diffusion en gelose, un dixieme de concentration minimale inhibitrice de DHSM augmenta l'activite de PEN 9 a 14 fois, alors que l'efficacite de DHSM fut multipliee d'un facteur de 3 a 7 par PEN. Ces resultats ont ete discutes en tenant compte du nombre probable de staphylocoques se trouvant dans la mamelle bovine lors de mastite chronique et en prenant en consideration les concentrations d'antibiotiques presentes dans les glandes mammaires de vaches traitees au tarissement. Les resultats obtenus expliquent l'excellent effet therapeutique de combinaisons de PEN et DHSM a hauts dosages contre les mastites a staphylocoques. Resumen Evaluacion cuantitativa in vitro de la actividad de la combinacion Benzilpenicilina y Dihidroestreptomicina sobre estafilococos aislados en cuarterones de vacas y sobre las actividades sinergisticas en particular 206 cepas Staph, aureus aisladas en muestras de leche fueron analizadas en cuanto a su sensibilidad frente a Benzilpenicilina (PEN) y Dihidroestreptomicina (DHSM). Ante una supuesta concentracion minima de inhibicion de 4.1 resp. 37 ppm, el 43% de las cepas bacterianas eran PEN-resistentes y el 33% DHSM-resistentes. El 97% de las cepas que eran PEN-resistentes producian penicilinasa. El tamano del inoculum tuvo un influjo importante sobre la sensibilidad frente al PEN de los estafilococos que eran PEN-resistentes. El influjo del tamano del inoculum sobre la sensibilidad frente al DHSM de las cepas que eran DHSM-resistentes era insignificante. La comparacion entre los porcentajes cumulativos de inhibicion de los antibioticos utilizados solos o en combinacion, y los analisis de las concentraciones de inhibicion fraccionadas (Fractional Inhibitory Concentrations) mostro indicios univocos de un efecto sinergistico significante por la combinacion PEN/DHSM. Este efecto sinergistico se expreso tambien en las cepas PEN- y DHSM-resistentes. Se contrasto la induccion de penicilinasa por PEN con ayuda de dos cepas PEN-resistentes. Resulto que la produccion de beta-lactamasa era disminuida a un deimo (1/10) por el simultaneo influjo del DHSM (PEN 100 unidades/ml, DHSM 100 ppm). En un ensayo de agardifusion un decimo de la concentracion minima de inhibicion de DHSM aumento la actividad de PEN de 9–14 veces, mientras que PEN elevo la eficacia de DHSM a la potencia 3–7. Los datos de estos estudios se refieren al numero esperado de estafilococos en los cuarterones de vacas en casos de mamitis cronicas y a las concentraciones de agentes quimicos despues del tratamiento. Los resultados ofrecen una explicacion por el buen efecto obtenido con tratamientos con alta dosis de PEN/DHSM; y tambien por los casos de mamitis provocadas por estafilococos resistentes.

Background: The purpose of the study was to examine whether penicillin-susceptible and nonsusceptible strains of Streptococcus pneumoniae exhibited different pharmacodynamic responses to benzylpenicillin. Methods: The postantibiotic effects (PAEs) and the postantibiotic sub-MIC effects (PA SMEs) were investigated by optical density against strains of S. pneumoniae with different susceptibilities to benzylpenicillin. To validate the data, the PAE and PA SME of one susceptible and one resistant strain were also tested with the viable count method. The post-MIC effects (PMEs) were studied in an in vitro kinetic model, simulating human pharmacokinetics with a half-life of 1 h and a time above MIC of approximately 20% of 24 h. Results: There were no differences with respect to the PAEs, PA SMEs and PMEs of benzylpenicillin for the various strains of S. pneumoniae, irrespective of their susceptibility to penicillin. For both some of the susceptible and resistant strains investigated, longer PA SMEs at 0.2 and 0.3 × MIC were noted, indicating that these parameters might be more dependent on the type of strain rather than on the susceptibility status. Conclusion: No differences in the pharmacodynamic response after similar drug exposure were seen for S. pneumoniae strains with different penicillin susceptibility.

Resume Objectif – Determiner l'etat de la resistance du pneumocoque en 1999 dans la region Rhone-Alpes. Patients et methodes – Mille huit cent treize souches de Streptococcus pneumoniae (64,5 % adultes, 35,5 % enfants) ont ete collectees par 31 laboratoires. La sensibilite a l'oxacilline des souches isolees en situation pathogene a ete mesuree (normes du CA-SFM). Pour toutes les souches de sensibilite diminuee a la penicilline G (PSDP), les CMI a la penicilline G, l'amoxicilline et au cefotaxime ont ete determinees (E-test ou ATB-Pneumo). Le centre coordinateur a controle la CMI ainsi que le serotypage des souches de PSDP. Resultats – La prevalence des PSDP etait de 40,5 %. Parmi les 9,4 % de resistants, 63,3 % etaient intermediaires a l'amoxicilline et 0,8 % resistants au cefotaxime. La resistance a l'erythromycine, tetracycline, cotrimoxazole, chloramphenicol, pristinamycine, rifampicine et fosfomycine etait de 42 %, 27,4 %, 37,9 %, 19,2 %, 1,4 %, 0,6 % et 8 %. La multiresistance chez les PSDP etait de : 70,7 % a l'erythromycine, 72 % a cotrimoxazole, 45 % a tetracycline, 32,8 % au chloramphenicol, 1,8 % a la pristinamycine et 0,4 % a la rifampicine. Les PSDP de serotypes 14 (23,8 %) etaient les plus frequents, puis les serotypes 6 (16 %), 23 (15,7 %), 19 (11 %), et 15 (2,8 %). Discussion – Depuis 1997 les PSDP augmentent (29,5 % versus 40,5 %), les souches resistantes a l'amoxicilline sont encore peu frequentes (2 %) et celles resistantes au cefotaxime (0,3 %) sont maintenant isolees.

Concentration of benzylpenicillin filtered broths purified by ultrafiltration and fermented broths clarified by ultrafiltration was carried out by reverse osmosis. This study was done using a reverse osmosis laboratory/pilot installation from Paterson Candy International Ltd. whose module has a tubular configuration and a membrane with a molecular weight cut-off of 100 Dalton (ZF99) made of a polyamide film with a rejection of 99% of NaCl. It was concluded that reverse osmosis is an adequate technique to concentrate benzylpenicillin ultrafiltered broths, leading to low losses of benzylpenicillin in the permeate and high benzylpenicillin recovery for high volumetric concentration factors.

A liquid chromatography method for analysis of benzylpenicillin was examined in a collaborative study involving seven laboratories. The method comprised an isocratic part, which is used in the assay. The isocratic part corresponds to the assay method for benzylpenicillin used by a manufacturer. When the isocratic part is combined with gradient elution, the method is suitable for purity control. Five samples of benzylpenicillin (sodium and potassium salts) were analysed. The main component and the impurities were determined. An analysis of variance proved the absence of consistent laboratory bias. The laboratory-sample interaction was not significant. Estimates for the repeatability and reproducibility of the method, expressed as standard deviations (S.D.) of the result of the determination of benzylpenicillin, were calculated to be 0.71 and 0.80, respectively.

The synthesis from penicillin G of a series of potent pseudosymmetric inhibitors 11 a-k of HIV-1 proteinase is described. The 2-pyridyl substituted compounds 11a and 11j showed improved antiviral activity compared to their C2-symmetric counterparts 3 and 4.

It has been shown that bacteria in a postantibiotic (PA) phase exposed to subinhibitory concentrations (sub-MICs) of antibiotics show a long delay before regrowth. This effect has been named the PA sub-MIC effect (PA SME). In the present study, we have used a new method to demonstrate this phenomenon. A computerized incubator for bacteria, Bioscreen C (Lab Systems, Helsinki, Finland), which incubates the bacteria, measures growth continuously by vertical photometry, processes the data, and provides a printout of the results was used. With this method, one may easily test several antibiotics against different bacteria for PA effects (PAEs), PA SMEs, and SMEs. In this study, the effects of benzylpenicillin against beta-hemolytic streptococci and pneumococci were examined. The bacteria were exposed to 2, 10, or 50x MIC for 2 h, washed and diluted, incubated in the Bioscreen C incubator, and then exposed to 0.1 to 0.9x MIC. The regrowth was monitored for 20 h. The PAE was calculated as the difference in the time required for the exposed and unexposed bacteria to grow to a defined point (A50) on the absorbance curve. A50 was defined as 50% of the maximum absorbance for the control cultures. The PA SMEs were calculated as the difference in the time required for the reexposed cultures and the unexposed controls to reach A50. The PAEs ranged between 0.6 and 3.2 h and varied little with the concentration used for the induction of the PAEs. At 0.2x MIC, the PA SMEs were 2 to 3 h longer than the PAEs. Higher sub-MICs increased this delay before regrowth. Most cultures exposed to sub-MICs alone were only slightly affected compared with the controls.

The reactive extraction (re-extraction) of penicillin G from reaction mixtures is based on complexation with a carrier and subsequent dissociation of the complex. An established mathematical model for this has been analysed to develop a feasibility domain within which the process may be designed and optimised. Geometric and physical interpretations of this domain are provided.

The mixed metabolism model of Nicolaiet al. (1991) has been used to analyse the sensitivity of fed-batch fermentation for penicillin G with respect to four parameters. The cases of fully endogenous, fully maintenance and mixed metabolisms have been studied. Sensitivities with respect to two parameters,K x andK i, were much larger than for the other two. Differences between the three kinds of metabolism were sharpest forK p. The implications of both observations are discussed.

In this paper, an updated unstructured mathematical model for the penicillin G fed-batch fermentation is proposed, in order to correct some physical and biochemical shortcomings in the model of Heijnen et al. (1979,Biotechnol. Bioeng.,21, 2175–2201) and the model of Bajpai and Reus (1980,J. Chem. Tech. Biotechnol.,30, 332–344). Its main features are the consistency for all values of the variables, and the ability to adequately describe different metabolic conditions of the mould. The model presented here can be considered as the translation of the latest advances in the biochemical knowledge of the penicillin biosynthesis.

Benzylpenicillin (PCG; 180 μmol/kg), a classic β-lactam antibiotic, was intravenously given to Sprague-Dawley (SD) rats and multidrug resistance-associated protein 2 (Mrp2)-deficient Eisai hyperbilirubinemic rats (EHBR). A percentage of the [3H]PCG was excreted into the bile of the rats within 60 min (SD rats: 31.7% and EHBR: 4.3%). Remarkably, a transient increase in the bile flow (∼2-fold) and a slight increase in the total biliary bilirubin excretion were observed in SD rats but not in the EHBR after PCG administration. This suggests that the biliary excretion of PCG and its choleretic effect are Mrp2-dependent. Positive correlations were observed between the biliary excretion rate of PCG and bile flow ( r2= 0.768) and more remarkably between the biliary excretion rate of GSH and bile flow ( r2= 0.968). No ATP-dependent uptake of [3H]PCG was observed in Mrp2-expressing Sf9 membrane vesicles, whereas other forms of Mrp2-substrate transport were stimulated in the presence of PCG. GSH efflux mediated by human MRP2 expressed in Madin-Darby canine kidney II cells was enhanced in the presence of PCG in a concentration-dependent manner. In conclusion, the choleretic effect of PCG is caused by the stimulation of biliary GSH efflux as well as the concentrative biliary excretion of PCG itself, both of which were Mrp2 dependent.

Objectives: The aim of this study was to investigate the temperature profile of home intravenous (iv) antibiotic reservoirs and the stability of 16 megaunits of benzylpenicillin sodium in 120 mL of sodium chloride 0.9% at constant and variable temperatures. Methods: A Tinytag computerized thermometer recorded temperatures every minute in the home iv antibiotic reservoir pouches of nine patients over a 24 h period. Similar bags containing benzylpenicillin sodium (16 megaunits) were maintained either at a constant 36degreesC, 26degreesC or 21-22degreesC or were worn in a pouch by five healthy volunteers for a 24 h period. Other bags were stored at 3-5degreesC for 10 days. The bags were sampled at timed intervals and benzylpenicillin concentrations assayed by HPLC. Results: Median temperatures recorded in the infusion bags worn by the nine patients were in the range 16.7-34.1degreesC. For infusion bags maintained at 36degreesC, 26degreesC and 21-22degreesC, the concentrations of benzylpenicillin dropped below 90% of the initial concentration at a mean time of 5 h 18 min, 12 h 54 min and 13 h 20 min, respectively, whereas for bags worn by the healthy volunteers the mean time for 10% loss of benzylpenicillin was 9 h 20 min. In contrast, at 3-5degreesC, concentrations of benzylpenicillin only dropped below 90% of the initial concentration at 8 days. Conclusions: Significant temperature-dependent degradation of benzylpenicillin occurs during continuous home iv antibiotic programme infusions, which could result in loss of efficacy.

Serum concentrations of penicillin were measured in children with rheumatic fever. The adequacy of the values after administration of 1.2 million units of benzathine penicillin G every 2 or 3 weeks was confirmed; the adequacy of a 4-week regimen was questionable. The administration of 0.6 million units every 3 weeks was found to be inadequate to maintain serum levels high enough for the secondary prophylaxis of rheumatic fever.

A rapid enzyme-linked immunosorbent assay (ELISA) for the detection of penicillin G in milk at concentrations of 6 ng/ml (0.01 IU/ml) was used to screen 1651 off-farm milk samples previously reported as containing no detectable levels of antimicrobial substances. Using a single-well per test format and a percent inhibition cut-off for the determination of positive/negative endpoint, 3.1% positives were obtained. Comparison with intra-assay standards lowered the numbers of positives to 0.42%. Analysis of 170 milk samples positive for antimicrobials confirmed 92.4% as containing penicillin G using the prescribed cut-off level and 87.6% when compared to standards. The ELISA, now available commercially in kit form, analyses between 1 and 48 samples in 15 minutes. It will detect 0.01 IU/ml to a level of confidence of 99% and 0.005 IU/ml with between 75 and 95% confidence.

Growth in the presence of 100 ppm benzylpenicillin (BP) for 2 h failed to result in a detectable reduction in cfu. Cells grown and incubated for 24 h in 0, 1, 10 and 100 ppm BP underwent reductions in cfu of 0%, 0%, 90% and 99% respectively of maximum cfu values.

Plasma penicillin levels were studied 2, 3, and 4 weeks after intramuscular benzathine penicillin G (BPG) doses of 1,200,000, 1,800,000, and 2,400,000 U. Proportions of patients with penicillin levels above 25 ng/ml at each week increased with increasing BPG dose. Further studies of higher-dose BPG for rheumatic fever prophylaxis are required.

The susceptibility to penicillin of 6 prevalent pneumococcal types isolated from nasopharynx in 1992 was compared with that of corresponding types from 1980–82. The 6 types or groups, 6, 9, 14, 15, 19 and 23, constituted 78% of consecutive isolates. 19/204 isolates in 1992 were intermediately resistant (MIC 0.12–1.0 mg/1) in comparison with 1/194 from 1980–82 (p < 0.001). Resistant strains (MIC ⩾ 2 mg/1) were not found. Of group 15, no fewer than 10/31 isolates were intermediately resistant, which may support the clonal origin and spread of penicillin-resistant pneumococci. At least 5.0% of nasopharyngeal isolates are now intermediately resistant to penicillin. This figure is substantially higher than the 2% earlier reported in Sweden.

The occurrence of a paradoxical effect of cloxacillin and benzylpenicillin in 7 strains of Staphylococcus aureus was studied with time killing curves in vitro. The isolates were exp

Practical procedures have been developed for synthesis of peptides using lipase as catalyst.

The kinetics of reextraction of penicillin from the LA-2-penicillin complex-n-butylacetate solution by phosphate buffer was investigated experimentally and theoretically. The concentration time functions can be described by a mathematical model in a wide range of pH-values and complex concentrations.

The degradation of several penicillins in unbuffered aqueous solution produces N-formylpenicillamine, in some cases in high yield. Very little or no penicillamine is formed under these conditions. N-Formylpenicillamine was produced from benzylpenicillin at pH values between 2.5 and 7, with a maximum yield of 30% at pH 5, whereas penicillamine was produced only at pH 5 or below in a yield of less than 1%. Benzylpenicillenic acid at pH 5 gave a 20% yield of N-formylpenicillamine and no penicillamine whereas benzylpenicilloic, penilloic and penillic acids gave no N-formylpenicillamine and a small amount of penicillamine.

We have studied the pharmacokinetics of intravenously administered benzylpenicillin in normal subjects during bedrest and during ambulation. The values of total body clearance, mean residence time, and renal clearance found during ambulation were 487.4 +/- 100.5 ml/min, 36.23 +/- 13.45 min, and 309.4 +/- 93.4 ml/min (means +/- SD). The corresponding values for bedrest were 543.6 +/- 122.6 ml/min, 35.27 +/- 10.21 min, and 324.1 +/- 145.3 ml/min. There were no significant differences between any of these pharmacokinetic variables with the change in posture. These results differ from previously reported results for the effects of posture on the pharmacokinetics of penicillins administered by extravascular routes, and suggest that the absorption of benzylpenicillin may be dependent on posture.

The reextraction of Penicillin G from the Penicillin-LA-2 complex in n-butyl acetate by phosphate buffer was investigated in a bench-scale Karr column. The influence of stroke frequency, pH-value and the throughput of the organic phase were studied. Penicillin V was extracted from fermentation broth and reextracted by phosphate buffer. The extraction is hampered by the proteins precipitated during the extraction. The elimination of this effect is discussed.

Resume Une deglobulisation consecutive a un auto-anticorps anti-erythrocytaire de nature IgG apparait chez une malade 5 jours apres la mise en route d'un traitement penicilline G-cefoperazone. L'etude serologique montre la responsabilite de la penicilline et l'absence d'antigenicite croisee de la cefoperazone avec le groupement BPO. A l'occasion de cette observation caracteristique, le mecanisme pathogenique d'une telle anemie est rappele, l'interet de la technique serologique sur auto-analyseur souligne ainsi que la precocite d'apparition de telle complication chez les sujets sensibilises.

Summary The pharmacokinetics of benzylpenicillin, cephapirin, cephacetrile, cloxacillin, amoxycillin, and ampicillin were studied in dairy cows after intravenous and intramuscular administration of the sodium salts of these drugs. The kinetics of benzylpenicillin were evaluated after intramuscular injection of penethamate hydriodide and several procaine penicillin G veterinary formulations. For a better estimation of the pre-slaughter withdrawal times for animal tissues after treatment with beta-lactam antibiotics, a new approach is proposed which is based on simultaneous determination of drug concentrations in muscle drip, kidney cortex, and in serum during the elimination phase of drug disposition. For each beta-lactam antibiotic product, a uniform muscle drip-to-serum concentration ratio was found. The rate of drug elimination from the muscle drip can thus serve as a basis for calculating the pre-slaughter withholding period for carcass meat at any desirable drug residue tolerance level. Examples for such calculated pre-slaughter withholding times for muscle and kidney tissues, based on kinetic values, are presented. Zusammenfassung uber die Ruckstandskinetik des Beta-Lactam Antibiotikums bei gesunden Milchkuhen Bei Milchkuhen wurde die Pharmakokinetik von Benzylpenicillin, Cephapirin, Cephacetril, Cloxacillin, Amoxycillin und Ampicillin (intravenose und intramuskulare Verabreichung der Natriumsalze) untersucht. Die Benzylpenicillin-Kinetik wurde nach intramuskularer Injektion des Penethamat Hydriodid und mehrerer Procain-Penicillin G-Veterinar-Formulationen gepruft. Zur besseren Festlegung der Eliminationszeiten bzw. Wartezeiten fur Schlachtvieh, das mit s-Lactam-Antibiotika behandelt wurde, wird eine neue Methode vorgeschlagen. Diese beruht auf der simultanen Messung der Medikamentenkonzentration im Muskelsaft, in der Nierenrinde und im Serum wahrend der Eliminationsphase. Fur jedes s-Lactam-Antibiotikum wurde ein bestimmtes Konzentrationsverhaltnis im Muskelsaft und Serum gefunden. Auf Grund der Eliminationsgeschwindigkeit kann die Wartezeit fur die Schlachtung berechnet werden. Anhand pharmakokinetischer Daten werden Wartezeiten-Beispiele wiedergegeben. Resume Sur la cynetique de residu de l'antibiotique s-lactam chez des vaches laitieres saines La pharmacocynetique de benzylpenicilline, cephapirine, cephacetrile, cloxacilline, amoxycilline et ampicilline a ete examinee chez des vaches laitieres apres application intraveineuse et intramusculaire des sels de sodium. La cynetique de la benzylpenicilline fut testee apres une injection intramusculaire veterinaire. On a formule une nouvelle methode pour ameliorer l'etablissement du temps d'elimination et d'attente pour le betail de boucherie traite avec un antibiotique s-lactam. Cette methode consiste a mesurer simultanement la concentration medicamenteusse dans le jus de viande, le cortex renal et le serum durant la phase d'elimination. On a trouve un rapport de concentration determine dans le jus de viande et le serum pour chaque antibiotique s-lactam. On peut calculer le delai d'abattage sur la base de la rapidite de l'elimination. Des exemples de temps d'attente sont donnes a l'aide de resultats pharmacocynetiques. Resumen Sobre la cinetica residual del antibiotico beta-lactam en vacas lecheras sanas Se analizo en vacas lecheras la cinetica farmacologica de penicilina bencilica, cefapirina, cefacetril, cloxacilina, amoxicilina y ampicilina (administracion intravenosa e intramuscular de las sales sodicas). La cinetica de la penicilina bencilica se evaluo tras inyeccion intramuscular del hidriodido de penetamato y varias formulaciones veterinarias de procaina-penecilina G. Se propone un metodo nuevo para estimar mejor los tiempos de eliminacion resp. los plazos de espera para reses de matadero, las cuales han sido tratadas con antibioticos s-lactam. Se basa este metodo en la medicion simultanea de la concentracion medicamentosa en el jugo muscular, corteza renal y suero sanguineo durante la fase de eliminacion. Para cada antibiotico s-lactam se hallo una relacion uniforme de concentracion en el jugo muscular y en el suero sanguineo. Con arreglo a la velocidad de eliminacion del jugo muscular se puede calcular el plazo de espera hasta la matanza. Con ayuda de datos farmacocineticos se presentan ejemplos de periodos de espera.