Diclofenac concentrations in synovial fluid and plasma after cutaneous application in inflammatory and degenerative joint disease.

1. Ten patients with bilateral knee joint effusions were treated topically with a gel containing 1 g diclofenac/100 g (80 mg three times daily). They were randomized to receive diclofenac gel to one knee and a placebo gel preparation to the other knee. 2. Diclofenac was assayed in synovial fluid and blood plasma by GC/ECD as the pentafluorobenzyl-ester derivative. 3. Total concentrations of diclofenac in synovial fluid (day 4) were significantly higher in the diclofenac gel treated knee than in the contralateral placebo treated knee (25.5 +/- 3.6 ng ml-1 vs 21.6 +/- 2 ng ml-1; P less than 0.05). These concentrations were lower than total plasma drug concentrations (40.6 +/- 4.7 ng ml-1, n = 10, P less than 0.01). Unbound concentrations of diclofenac in synovial fluid from either the diclofenac gel treated or the placebo treated knee were not significantly different from each other or from plasma free concentrations (115 +/- 16 and 99 +/- 12 vs 108 +/- 19 pg ml-1). 4. Clinical parameters showed improvement of joint mobility and a small reduction of swelling (circumference) in both knees with time. However, the differences between knees were not significant. 5. We conclude that direct transport of diclofenac from the skin into the ipsilateral knee joint after cutaneous application is minimal. Distribution seems to be predominantly via the blood. Whether the observed improvements of clinical parameters were due to drug effects or to the spontaneous course of the underlying disease cannot be distinguished.

[The prevention and control of salmonellosis in cattle and swine]. / Die Verhütung und Bekämpfung der Salmonellosen bei Rind und Schwein.

The control of salmonellosis in the national livestock of the GDR is carried through on the basis of central regulations issued by the Head of the Veterinary Service. The crucial points of these programmes are zoo-sanitary, organizational and immunoprophylactic measures. The effectiveness of the immunoprophylaxis against salmonellosis in cattle and pigs has increased after using live vaccines. At present, the elimination of the host-adapted serovars and the decrease of serovars important for infections in man is focused on. Particular attention is payed to the serovars S. typhimurium and S. enteritidis. The objective requires a well coordinated cooperation between the Veterinary Service and the Public Health Service.

[The reference values of the hemoglobin content, the hematocrit and the mean concentration of corpuscular hemoglobin of calves reared without iron substitution. 1. Dependence on the rearing period]. / Referenzwerte des Hämoglobingehalts, des Hämatokrits und der mittleren korpuskulären Hämoglobinkonzentration bei Aufzuchtkälbern ohne Eisensubstitution. 1. Mitteilung. Abhängigkeit vom Haltungsbereich.

A total of 1.088 blood samples (1 to 6 per animal) were taken from 491 rearing calves in the colostral period, the milk feeding period and the weaning period (at the age of 4, 22, 51, 79, 105, 122 and 145 days); the hemoglobin content (Hb), the hematocrit (Hc) resp. the mean corpuscular hemoglobin concentration (MCHC) were determined resp. calculated. Hb, Hc and MCHC were drawn in diagrams in dependence on the rearing period as arithmetic means with standard deviations, as quartiles and as frequency distributions on an interval scale. During the rearing periods with milk feeding the anaemic frequency was considerable. Anaemia resp. hypochromia frequency had an inverse relation to the developing increase of concentrated feed and roughage consumption and thus makes it probable that the cause of anaemia is the intake and/or absorption of iron insufficient for the weight gain performance achieved. The consumption of solid feed by the hematologically examined calves developed more quickly than in other GDR rearing farms due to the early ad libitum supply with this feed component and the composition of fluid feed with milk. Reference is made that the frequency of hypoferric anaemia can also be considerable during the milk feeding period in the intensive rearing of lambs and kids if an effective iron intervention is not made.

[Investigations of anemia of male rearing calves. 4. Relations between weight at birth, duration of keeping and increase of the ive weight in the period of the calves being fed on colostrum as well as the count erythrocytes in the weaning period of the calves]. / Untersuchungen zur Anämie bei männlichen Aufzuchtkälbern. 4. Mitteilung. Abhängigkeiten zwischen Geburtsmasse, Haltungsdauer und Lebendmassezuwachs im Kolostralkälberbereich sowie rotem Blutbild im Tränkkälberbereich.

With 195 male rearing calves which received concentrates ad libitum beside fluid feed with milk from their 5th day of life onward, investigations were made if and how far the characteristics of the development of the calves while they are fed on colostrum (body weight at birth, live weight increase and duration of keeping or stalling age) correlate with the hemoglobin content (Hb), the hematocrit (Hc) and the average corpuscular hemoglobin concentration (MCHC) of the animals on the 3rd, 28th resp. 56th day of keeping in the weaning period. There was a significant simple dependence particularly between body weight at birth, live weight increase and stalling age on the one hand and the hematologic values on the 3rd day of keeping in the weaning period on the other. A partial correlation analysis showed that the live weight increase while the calves were fed on colostrum was the main variable for all three hematologic parameters at the beginning of the weaning period of the calves. With increasing live weight, Hb, Hc and MCHC were diminished. This analysis was supplemented by the results of a cross--section investigation of the development of the milk and concentrate consumption and the Fe-intake of the calves fed on colostrum. The calculation of the Fe-balance showed that the mere ad libitum supply with feed supplements rich in Fe cannot prevent Fe-deficiency. Anaemia developing in the first month of the calves' lives is not a physiologic one but essentially caused by Fe-deficiency.

Bio-availability and pharmacokinetics of cyproterone acetate-14C and ethinyloestradiol-3H after oral administration as a coated tablet (SH B 209 AB).

PIP: Bioavailability and pharmacokinetics of carbon-14-cyproterone acetate-methylene (2 mg) and tritiated ethinyl estradiol (50 mg) after oral administration as a coated tablet (SH B 209 AB) were investigated. 8 women received the compounds, and carbon-14 and tritium activity in plasma, urine, and feces was determined up to 7 or 10 days postadministration. Cyproterone acetate was completely absorbed. The maximum plasma level was reached in 30 minutes to 3 hours, when 2.2% of the dose was found in total plasma corresponding to 24 ng eq/ml. The plasma level decreased with a 1/2-life of 7.9 hours (distribution and elimination) and later with a 1/2-life of 2.5 days (elimination). Elimination via urine was 37% and up to Day 10 postadministration 91% of the dose was found in urine and feces. Ethinyl estradiol was adsorbed very rapidly and almost completely with the maximum plasma level reached in 60 minutes. At this time 10% of the dose was found in the plasma corresponding to 2.1 ng eq/ml. The plasma level dropped up to about 8 hours postadministration with a 1/2-life of 5.1 hours and later with a 1/2-life of 27 hours. Ethinyl estradiol was eliminated in urine and feces in the ratio of 4:6 and 91% of the dose was recovered.^ieng

[Pharmacokinetics of cyproterone acetate in normal subjects after i.m. and oral application (author's transl)]. / Pharmakokinetik von Cyproteronacetat bei gesunden Probanden nach intramuskulärer und oraler Applikation

Sixteen volunteers were given cyproterone acetate-2'-14C (6-chloro-17-hydroxy-1alpha,2alpha-methylene-pregna-4,6-diene-3,20-dione acetate; Androcur¿) in single doses of between 2 and 12 mg i.m. and p.o. in 19 investigations. The plasma radioactivity was then determined at suitable intervals. Urine and faeces were collected quantitatively for 12 days. After oral administration the highest concentrations in plasma were found 1--4 h after administration. The mean amounts were 2--3% of the administered dose in the plasma volume. Plasma concentrations of more than half the highest values were measured for a period of 2--8 h. Cyproterone acetate was eliminated from the body with a half-life of about 1 1/2 days for men and about 2 days for women. After oral administration in single doses of 2--12 mg the compound was almost completely absorbed.

[Bioavailability and pharmacokinetics of 14C-cyproterone acetate after administration as a 50-mg tablet (author's transl)]. / Bioverfügbarkeit und Pharmakokinetik von 14C-Cyproteronacetat nach Applikation als 50-mg-Tablette

Four male volunteers were each given a 50 mg oral dose of methylene-14C-labelled cyproterone acetate in a formulation largely identical to the commercial preparation Androcur Tablets. A further 3 volunteers were each given 10 mg of the 14C-labelled compound by intramuscular injection. Plasma samples were obtained and urine and faeces collected quantitatively from each volunteer up to 10 days post administration. 1. Absorption of the 50 mg of cyproterone acetate administered in the form of Androcur Tablets was largely complete. 2. The maximal plasma level of 400 +/- 40 ng cyproterone acetate equivalents/ml of plasma, calculated from the 14C activity, was found 3,8 +/- 0,5 hours after oral administration. By 10 hours post administration the plasma level had declined with a half-life of 7,9 +/- 2,5 hours (distribution and elimination). The fictitious distribution volume assignable to this process amounted to 140 +/- 40% of body weight. Plasma 14C-activity then decreased with a half-life of 1,8 +/- 0,2 days, which was consistent with elimination. 3. The labelled substance was almost completely extractable from plasma and could be separated by chromatography into 2 fractions of about equal size: cyproterone acetate and one metabolite. 4. Orally administered cyproterone acetate was eliminated with a half-life of 1,6 +/- 0,1 days. By 10 days post administration 33 +/- 6% of the dose had been detected in urine and 60 +/- 8% in faeces. Up to this time total elimination amounted to 93 +/- 5% of the dose. 5. After intramuscular injection of 10 mg of cyproterone acetate the half-life for absorption from the muscular depot was 7,0 +/- 0,2 hours. Between 2 and 10 days post administration there was a uniform decrease in plasma level and urinary elimination with half-life of 2,3 +/- 0,1 days and 2,1 +/- 0,2 days respectively. By the end of the trial 34 +/- 5% of the dose had been eliminated with urine and 57 +/- 6% with faeces.