[Initial clinical experience with taurolidin instillation into the area of the middle area]. / Erste klinische Erfahrung mit Taurolidininstillationen im Mittelohrbereich.

In this pilot study 2% taurolidin solution was used for irrigation of infected ears and instillation topically in 10 patients with severe purulent otitis media. The main purpose of the study was to find out whether the application of the taurolidin solution into the middle ear would cause significant pain or not. A slight increase in local pain was found sporadically but was not reason for withdrawing the drug. Twelve of 13 bacterial species isolated prior to treatment were eliminated during the trial, with the otorrhea of most patients stopping after just the first instillation. Audiometric evaluations during and 30 months after therapy did not reveal any ototoxic side effects. Tinnitus was not experienced by any patient during therapy. Overall findings demonstrated that local therapy with taurolidin for patients with severe purulent otitis media was very well tolerated and effective bacteriologically. There were also no therapy-related complications or ototoxic side effects.

[Investigations on the pharmacokinetics of apalcillin in man]. / Untersuchungen zur Pharmakokinetik von Apalcillin beim Menschen.

Plasma levels and urinary excretion was studied after i.v. bolus of 1000 mg (2S,5R,6R)-6-[(R)-2-(4-hydroxy-1, 5-naphthyridine-3-carboxamido)-phenylacetamido]-3, 3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid (apalcillin, PC-904) and after long-term infusion of 3000 mg apalcillin in volunteers of both sexes. For measuring the concentrations a cylinder agar diffusion test was used. The plasma levels decreased from 150 microgram/ml 2 min after injection to 100 microgram/ml 15 min p.a. and to 37 microgram/ml after 90 min. For the terminal half-life of elimination from plasma a value of 1.0 was calculated. After termination of the long-term infusion concentrations of 70-80 microgram/ml were found in plasma. In this case a terminal half-life of 1.5 h was calculated. Due to the fast half-life of elimination no cumulation will occur in the case of repetitive dosing. This suggestion is supported by the finding, that the mean transit time of 1.4 h is very short. On the other hand the substance is distributed so rapidly that therapeutic levels are reached 30 min after infusion. Using data from literature, a proportionality between dose and area under the plasma curve could be demonstrated in the range 1000-3000 mg apalcillin. Our results show that about 20% of the dose administered is found in urine. 10 h after application the urinary excretion is finished. No side effects were observed during the acute assays.

[Investigations on antibacterial activity of apalcillin]. / Untersuchungen zur antibakteriellen Aktivität von Apalcillin.

In 201 clinical isolates the antibacterial activity of (2S,5R, 6R)-6-[(R)-2-(4-Hydroxy-1,5-naphthyridine-3-carboxamido) -2-phenylacetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo [3.2.0]heptane-2-carbonic acid (apalcillin, PC-904) a new semisynthetic broad spectrum penicillin, was tested. The activity was almost equal to piperacillin, the at present optimal penicillin derivative, but against pseudomonas apalcillin was clearly superior. Lack of activity as compared to the acylureidopenicillins was found in proteus species whilst its activity against E. coli and klebsiella species was higher. Antagonism was observed in pseudomonas aeruginosa for the combination of apalcillin and cefoxitin which also existed with azlocillin or piperacillin and cefoxitin.

Pirenzepin in gastric and duodenal ulcer: a double-blind trial.

In seventy-five out-patients with gastric and duodenal ulcer a comparative double-blind trial with pirenzepin against placebo was performed. The dose was 50 mg pirenzepin daily or placebo respectively, the duration of treatment being 4 weeks. The healing effect of pirenzepin in duodenal ulcer patients could be proven endoscopically and was statistically significant when compared with placebo (p less than or equal to 0.05). Strong evidence for the therapeutic efficacy of pirenzepin could be further demonstrated in both duodenal and gastric ulcer patients by measuring the marked reduction of ulcer size, even though statistical difference against placebo in gastric ulcers was not fully achieved. Pirenzepin was well tolerated by all patients, except for a mild case of diarrhoea which occurred in one patient. No patient complained of dryness of the mouth or of blurred vision.

Plotting regression lines for a new beta-lactam antibiotic (mecillinam).

Regression lines for mecillinam (FL 1060) were established according to the recommendations of th ICS. The investigation involved 477 Gram-negative and Gram-positive organisms with the widest possible spectrum of sensitivity which were isolated from fresh material for examination. Solid and liquid Müller-Hinton media (Merck and BBL) were used as nutrient media. The Difco Müller-Hinton medium is not suitable for this subtance because of the high ionic content. A general regression line for mecillinam is not admissible. The considerably restricted sphere of indication shown by our studies is presented with reference to the blood levels attainable in vivo. At the same time, the good sensivity of salmonella is pointed out.

[Studies on the pharmacokinetic equivalence of pivampicillin base and hydrochloride in capsules and tablets (author's transl)]. / Untersuchungen zur pharmakokinetischen Aquivalenz von Pivampicillinbase und -hydrochlorid in Kapseln und Tabletten

Absorption and urinary excretion of pivampicillin as hydrochloride and as base were studied following administration of four different formulations to 12 healthy volunteers in a cross-over study. A fluorimetric assay of ampicillin was adapted to be used with an Auto Analyzer system. The plasma concentrations observed are comparable to those reported in the literature. The amount of drug absorbed is the same for all four medications whereas absorption is more rapid from tablets than from capsules. Base and hydrochloride of pivampicillin are equivalent with respect to pharmacokinetic behaviour. So, the formulation itself seems to be more important for biological equivalence than the ionisation of the drug used in the formulation.