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Effects of long-acting steroid contraceptives on ovarian and uterine histology of rats.

Subcutaneous injection of single doses (5 to 20 mg/kg) of DMPA or NE in virgin female rats caused reduction in number and diameter of CL, and increase in number of atretic and cystic follicles in the ovary. Histological examination of the endometrium of these animals showed low cubiodal cells with sparse distribution of low columnar cells, glands with atrophic changes and compact uterine stroma with or without patches of oedema. The results suggest regressive and atrophic changes in the ovary and endometrium.

Animals↗

[The use of gentamicin-polymethylmethacrylate chains for the treatment of soft-tissue wounds in the region of the urinary tract (author's transl)].

Bactericidal concentrations of gentamicin can be attained by implanting at the site of the infection pellet chains of gentamicin-polymethylmethacrylate (PMMA) that permit the protracted release of the antibiotic for several weeks. Satisfactory healing of the wound was achieved in two cases of extensively infected soft-tissue wounds in the region of the urinary tract after temporary implantation of gentamicin-PMMA chains.

Adolescent↗

Comparative effects of placebo and plain and slow-release tablets of xanthinol nicotinate on exercise tolerance in normal human subjects.

The effects of placebo and plain and slow-release xanthinol nicotinate on exercise tolerance were studied in 6 normal human subjects. Placebo administration had no significant effect on exercise tolerance. Administration of plain and slow-release xanthinol nicotinate significantly increased exercise tolerance at 1 hour and 1--9 hours respectively from ingestion of the drug. The intensity and duration of action correlated well with the blood levels of nicotinic acid reported earlier. Four subjects experienced moderate to severe side-effects with plain xanthinol nicotinate. Only 1 subject experienced mild side-effects with slow-release xanthinol nicotinate. Slow-release tablets of xanthinol nicotinate may prove useful in the treatment of angina pectoris.

Adolescent↗

Comparison of soft gelatin capsule vs. sustained release formulation of papaverine HCl: vasodilation and plasma levels.

The vasodilatory action, plasma papaverine levels achieved, and the incidence of side effects after oral administration of papaverine hydrochloride as a soft gelatin capsule, were compared to those of a sustained release formulation. The incidence of side effects observed after 150 mg, two or three times per day, of the soft gelatin capsule was similar to that observed after 150 mg, twice per day, of the sustained release form in 15 patients with arteriosclerosis obliterans. A relatively higher plasma papaverine concentration was achieved, 120 minutes after 150 mg administration of the soft gelatin form, compared to an equivalent dose of the sustained release form. The degree of vasodilation obtained after four doses (150 mg X 4) of soft gelatin within 24 hrs., was significantly superior than that induced after four doses (150 mg X 4) of the sustained release form in 6 patients with a severe degree of arteriosclerosis obliterans.

Adult↗

Quinidine syncope: torsade de pointes with low quinidine plasma concentrations.

In 2 patients without clinically significant ischemic heart diseases, oral quinidine was used to control supraventricular arrhythmias. In both patients, syncopal attacks occurred, caused by a particular type of ventricular tachyarrhythmia called torsades de pointes. Quinidine plasma concentrations were low (2.6 and 1.2 mg/1, respectively); QRS duration was normal, but the Q-T interval was markedly prolonged.

Aged↗

Slow-K -- follow-up.

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Delayed-Action Preparations↗

[Clinical experience with sustained release cephalexin (S-6437) in pediatrics (author's transl)].

S-6437 (Sustained release cephalexin granule for pediatric use) was studied with the following results: 1) Following the single oral administration of 25 mg/kg of S-6437 in 6 children 4 approximately 6 years old, the following blood levels (average) of cephalexin were obtained: 3.1 microgram/ml in one hour after the administration, 8.6 microgram/ml in 2 hours, 8.7 in 4 hours, 7.2 in 6 hours, 4.0 in 8 hours and 1.2 in 12 hours. Effective blood levels of cephalexin by S-6437 were maintained for longer period of time than those by regular cephalexine dry syrup. In 4 of 6 children receiving S-6437, cephalexin was scarcely detected in their blood in 12 hours after the administration. From this, it is not considered that S-6437 is accumulated in body. 2) S-6437 was administered to 38 patients including: 7 with pneumonia, 7 with acute bronchitis, 1 with suppurative lymphadenitis, 4 with acute pharyngitis, 15 with acute tonsillitis and 4 with acute urinary tract infections. Out of the 35 cases, 31 (88.6%) responded to S-6437, and 3 cases could not be evaluated. 3) Transient diarrhea in 2 patients, rash in 1 and elevation of serum GOT, GPT and LDH in 1 were observed. However, these side effects were improved by discontinuation of S-6437.

Age Factors↗

[Zollinger-Ellison syndrome treated medically by an inhibitor of H2 histamine receptors].

Metiamide an histamine H2-receptors antagonist has been used to treat a case of Zollinger-Ellison syndrome characterized by a long standing diarrhea, an important gastric hypersecretion and a moderatly elevated plasma gastrin but without digestive ulceration. At the dose of 600 mg per day, Metiamide induced a complete suppression of acid secretion, an effect which lasted for 15 days after stopping the drug. Accordingly and since the only finding at time of laparotomy was a small lymph node enlarged with endocrine metastatic tissue, the stomach was left intact and Metiamide pursued. During the first 4 months of chronic administration of Metiamide, acid secretion was maintained at levels below 25 p.cent of initial values. Ulteriorly however, although dosages of Metiamide were increased, acid hypersecretion resumed and a duodenal ulcer developed. Total gastrectomy was then performed 11 months after the beginning of Metiamide. In spite of the failure of Metiamide treatment, the long term follow up of this case of Zollinger-Ellison Syndrome, allowed us to get theoretical and practical informations.

Adult↗

[Drug-drug interactions (author's transl)].

This short outline of drug-drug interactions does not claim to cover the entire field. The task of this paper is to illustrate the most important principles of drug-drug interactions by paradigms taken from the experience of the practitioner. One consequence of drug-drug interactions is the change in pharmacolinetic parameters important for the therapeutical effect of drugs in the organism. Very often the elucidation of the mechanisms of drug-drug interactions in man is impossible; therefore, for clinical pharmacologists experiments on animals remain the tool in order to gain more knowledge in this field.

Age Factors↗

[Galenical possibilities and problems in protraction of drug effects (author's transl)].

In recent years, dosage forms with sustained release have obtained a significant importance. The technological possibilities for manufacturing are described as coating, embedding and matrix procedures. The range of auxiliary substances, which are responsible for the retardation of drug activity, reaches from lipophilic compounds as lipoids, fatty alcohols and compounds which are forming hydrogels as cellulose derivatives and natural polysaccharides to synthetic polymers derived from acrylic acid. The formulation of the dosage forms requires particular care in respect to the amount of initial and maintenance doses. On account of technological processes, for example during manufacturing of tablets, under certain circumstances the liberation rate is altered. In vitro test methods allow comparisons only then when the results can be counter-checked by in vitro experiments. The release of drug follows different mechanisms, which are described, entirely or in part, to be reactions following the time law of zero or first order. In special cases, a linear correlation is observed as a function of square root of time. The calculation of given special equations for events within the dosage form is feasible from blood-level values.

Biological Availability↗

[The influence of neuroleptic drugs on urinary excretion of non-protein nitrogen (author's transl)].

During treatment with thioxanthenes or phenothiazines of schizophrenic patients non-protein nitrogen in urine was measured. The values were calculated in relation to the excretion of creatinine. a) Flupentixol or fluphenazine applied in optimal dosage, increased the excretion of urea and the amino acids asp, glu + gln, and gly. b) Moreover, if the drug induced a parkinsonoid (thioridazine) the excretion of ser and thr was increased, too. The usual desalting procedure by ion-exchanging resins before chromatography increases the contents of several amino acids, e.g. asp, asn, ala, gly, cys, ser, thr, indicating a breakdown of some instable products.

Amino Acids↗