A study relating to bioavailability and renal elimination of bismuth after oral administration of basic bismuth nitrate.

The extent to which bismuth is absorbed following single and multiple oral administration of basic bismuth nitrate was investigated in healthy male subjects. The blood concentration of bismuth and the amounts excreted in urine and feces were determined. The results show that only a small fraction of the administered bismuth dose given in this form is absorbed. Existing differences in the absorption kinetics between this relatively insoluble bismuth salt and colloidal bismuth citrate are discussed.

[Pharmacokinetics of theophylline. Repeated single evening administration of Pulmo-Timelets slow-release capsules in comparison with theophylline slow-release tablets]. / Pharmakokinetik von Theophyllin. Wiederholte einmal abendliche Gabe von Pulmo-Timelets Retardkapseln im Vergleich zu einer Theophyllin-Retardtablette.

In an open randomized cross-over study involving a total of 12 healthy male subjects (mean age: 29 years), the pharmacokinetic profile of Pulmo-Timelets was compared with that of a theophylline controlled-release tablet (each administered at a dose of 600 mg theophylline in the controlled-release form) in the steady state after saturation with a single evening application over 4 days. The relative bioavailability of Pulmo-Timelets vis-a-vis the reference preparation referred to the area under the curve (AUC) in the 24-hour dosage interval, revealed a figure of 82%. Here, the reduced AUC manifested in particular in the absence of concentration peaks associated with a tendency towards somewhat higher plasma concentration 24 hours after administration. While the minima of the plasma concentrations were approximately comparable (mean values 24 hours after the last administration 9.3 and 8.2 mg/l for Pulmo-Timelets and reference preparation, respectively, the maximum concentrations after administration of the reference preparation (average 24.4 mg/l) were about 50% higher than after Pulmo-Timelets (16.3 mg/l). In the case of Pulmo-Timelets throughout the whole period, theophylline plasma concentrations were seen that were in very good agreement with the desired therapeutic range, while, in the case of the reference preparation, definitely and significantly higher concentration peaks occurred in the potentially toxic range.

Bioavailability of controlled-release metoclopramide. 1st communication: single dose study.

The bioavailability of metoclopramide monochloride hydrate after single dose oral administration of a controlled-release capsule (Gastro-Timelets) was compared with that of oral metoclopramide monochloride hydrate solution in four normal volunteers. 30 mg of each product was administered to each subject in a cross-over manner on two separate occasions and plasma metoclopramide levels were measured using a HPLC method. Although peak plasma metoclopramide concentrations were lower, and occurred later after capsule treatment than after solution, analysis of the area under the plasma concentration-time curve (AUC) values for the two formulations demonstrated that the products were equivalent in terms of the extent of absorption, with the mean AUC value (0-30 h) for the capsule 943.7 ng/h/ml and that for the solution 896.2 ng/h/ml.

Bioavailability of controlled-release metoclopramide. 2nd communication: multiple dose study.

The bioavailability of metoclopramide monochloride hydrate after oral multidose administration of controlled-release metoclopramide capsules (Gastro-Timelets) was compared with that of oral metoclopramide monochloride hydrate solution in 10 healthy men. 30 mg of each product was administered to each subject in a cross-over fashion for 5 consecutive days and the plasma metoclopramide concentration was measured using a HPLC assay. Peak plasma metoclopramide levels were lower, and occurred later after controlled-release capsules administration than after solution. The graphs representing plasma metoclopramide levels after controlled-release formulation were smooth and devoid of sharp peaks and troughs. The area under the plasma metoclopramide level-time curve (AUC) values showed that the products were bioequivalent with the mean AUC values for the capsule (0-24 h) 837.9 ng/h/ml and (120-150 h) 993.2 ng/h/ml; and for the solution (0-24 h) 878.8 ng/h/ml and (120-150 h) 1054.0 ng/h/ml.

Acute toxicity and analgesic action of a combination of buclizine, codeine and paracetamol ('Migraleve') in tablet and suppository form in rats.

Studies in rats were carried out to determine the acute toxicity and analgesic effect of a combination preparation ('Migraleve') containing codeine and paracetamol and the individual analgesics when given orally or by rectal administration. The results showed that the combination was no more toxic than paracetamol alone and, on the basis of the LD50:ED50 ratio, was less toxic by the oral than by the rectal route. In the rat-tail test, the combination induced a well-defined dose-dependent analgesic response which was greater after rectal administration. Codeine and paracetamol tested individually were effective only at relatively high dosage and, like the combination, their analgesic effects were greater after rectal administration and more clearly dose-dependent than after oral administration. Comparison of the area under the time-effect curves for the combination and the individual components confirmed the synergism between codeine and paracetamol.

Studies on the pharmacokinetics of fluorescein and its dilaurate ester under the conditions of the fluorescein dilaurate test.

Some aspects of the pharmacokinetics of fluorescein have been studied under the conditions of the fluorescein dilaurate test (Pancreolauryl-Test) in healthy volunteers. Dependence of fluorescein excretion on urine volume was investigated in a retrospective study in 370 patients. For intravenously administered fluorescein mean Cmax was 10.9 micrograms/ml with a mean elimination half-life of 286 min. For orally administered fluorescein sodium mean Cmax was 3.5 micrograms/ml with a tmax of 120 min and a t 1/2 of 267 min. Bioavailability of fluorescein by oral administration was 99%. By contrast, fluorescein from fluorescein dilaurate showed a 56% bioavailability under the conditions of the test with a Cmax of 1.8 micrograms/ml, a tmax of 270 min and a tt 1/2 of 246 min. Following enteral absorption of fluorescein hepatic extraction and enterohepatic circulation via the bile occurs, but although the concentrations of fluorescein in the bile may exceed those in the urine the absolute amount is likely to be small. In spite of the enterohepatic circulation fluorescein cleared from the urine within 24 h indicating that no delay between Part 1 and Part 2 of the test seems necessary. However, an adequate urine flow must be maintained throughout the test since a renal clearance/urine flow relationship exists, with fluorescein excretion being increased with increasing urine volume.

[Detection of ureolytic bacteria in urine in urinary calculi]. / Nachweis harnstoffspaltender Keime im Urin bei Urolithiasis.

Detection of ureolytic bacteria in the urine of stone patients: using a very sensitive and selective indicator medium we tested the urine of 308 stone patients for ureolytic bacteria. Urease-producing bacteria were found in 41 patients. In the urine of 13 of these patients we found more than 10(4) bacteria/ml and in 28 patients 10(4) or less. 75% of the patients with a positive urease test had infection stones. We believe, that the test for urease is a convenient and necessary completion of the bacteriologic-diagnostic measures.

[Detection of ureolytic bacteria in the urine of stone patients (author's transl)]. / Nachweis harnstoffspaltender Keime im Urin bei Steinpatienten.

Using a very sensitive and selective indicator medium we tested the urine of 308 stone patients for ureolytic bacteria. Urease-producing bacteria were found in 41 patients. In the urine of 13 of these patients we found more than 10(4) bacteria/ml and in 28 patients 10(4) or less. 75% of the patients with a positive urease test had infection stones. We believe that the test for urease is a convenient and necessary completion of the bacteriologic-diagnostic measures.

[Results of clinical trials with the cation exchange preparation campanyl in the therapy and metaphylaxis of calcium-containing urinary calculi (author's transl)]. / Ergebnisse klinischer Prüfungen des Kationenaustauscherpräparates Campanyl in der Therapie und Metaphylaxe calciumhaltiger Harnsteine.

The efficacy of the cation exchange preparation Campanyl (T1286) was tested in the treatment and metaphylaxis of calcium-containing urinary calculi. For this purpose, in vitro experiments, animal exeriments, orienting clinical studies in 79 patients, and a long term clinical trial in 42 patients over 12 months were undertaken; 22 of the latter patients are also still being treated with the cation exchange preparation, the observation period for 15 patients being 3 1/2 years and 2 1/2 years for 7 patients. As a result of these studies a lowering of the medium calcium excretion and a reduction of calculus discharge by more than half was achieved in the patients being treated with the cation exchanger, without restriction of calcium in the diet. There was not yet seen litholysis. Serious side effects or an influence on the serum electrolytes was not recorded with Campanyl (T1286).