Plafibride tolerance trial at increasing doses in healthy volunteers.

Tolerance of N-2-(p-chlorophenoxy)-isobutyryl-N'-morpholinomethylurea (plafibride ITA 104), was studied in a group of healthy volunteers. Bis[2-(p-chlorophenoxy)-2-methylpropionato]-hydroxyaluminum (alufibrate) was used as a reference drug. Treatment with both drugs was carried out at progressively increasing doses from 50 to 1600 mg/d. Both products were administered p.o. Plafibride showed a platelet antiaggregant effect at the dose of 800 mg/d, which was more evident at the dose of 1600 mg/d. Alufibrate showed no platelet antiaggregant effect. Both drugs showed a similar type of hypolipemic effect which was a little higher in the case of alufibrate. No side effects of any kind were noticed with either of the two drugs.

Plafibride tolerance trial in healthy volunteers.

Tolerance of N-2-(p-chlorophenoxy)-isobutyryl-N'-morpholinomethylurea (plafibride, ITA 104) administered over a 3-month period was studied in a group of healthy volunteers. Acetylsalicylic acid (ASA) was used as a reference drug. Both drugs were administered p.o. at the dose of 1600 mg/d. Plafibride showed a platelet antiaggregant effect similar in intensity to that shown by ASA, but its gastrointestinal tolerance was better. In the same way, plafibride showed a hypolipemic effect which was characterized by a decrease in the plasma level of total lipids and triglycerides and also by a drop in the percentage of the pre-beta-fraction of the lipoproteinogram at the expense of an increase in the alpha-fraction. No rebound effect was noticed when administration of the drug was stopped. The tolerance of plafibride was very good, both from the clinical and analytical point of view.

Clinical trials of plafibride in geriatric patients.

During a period of 15 days, 90 geriatric patients with various disturbances in blood lipids and manifestations of cerebral arteriosclerosis ingested 1200 mg/d of N-2-(p-chlorophenoxy)-isobutryl-N'-morpholinomethylurea (plafibride, ITA 104). Its significant activity in decreasing the pre-beta-lipoproteins and increasing alpha-lipoproteins was demonstrated. At the same time plafibride inhibited platelet aggregation by 50%. The activity of plafibride was compared to those of clofibrate and the inactive placebo. A similar experiment was carried out with 44 geriatric patients comparing the clinico-therapeutic and biochemical benefits of plafibride in relation to clofibrate and acetylsalicylic acid (ASA). Apart from the biochemical results, the symptomatologic and eletroencephalographical results of the patients treated with plafibride was more significant and positive than with the other drugs. Plafibride also showed better gastric tolerance and a lower incidence of collateral effects than did clofibrate and ASA.

Plafibride: clinical trial of a new platelet antiaggregating agent.

A clinical study with a new anti-aggregant preparation; N-2-(p-chlorophenoxy)-isobutyryl-N'-morpholinomethylurea (plafibride, ITA 104), is shown in this paper. A double blind study, was carried out comparing its effects with those of a well known antiaggregant agent, dipyridamole. No clinical nor analytical side effects of importance were observed.

Double-blind study on the activity of plafibride in the treatment of type IV hyperlipoproteinemia.

The effects of a new drug, N-2-(p-chlorophenoxy)-isobutyryl-N'-morpholinomethylurea (plafibride, ITA 104), were studied in a double blind study lasting four months on a group of 30 patients with a type IV hyperlipoproteinemia. In the patients treated with the active drug significant reductions in blood triglycerides were obtained, with a trend to normal. Reduction in blood cholesterol was inconsistent and not significant. As for the lipoproteinogram, a tendency towards a decrease in the pre-beta-lipoprotein fraction was observed and so was a non-significant tendency towards an increase in the alpha- and beta-lipoprotein fractions. Studies on the platelet functioning showed an obvious decrease in platelet aggregation in those patients treated with the active drug. This was very evident for the ADP and adrenaline inductors and rather less significant for collagen. Neither platelet adhesiveness nor aggregation rate changed. Tolerance of the drug was generally excellent. In one patient a decrease in some palpebral xanthelasmas was observed after two months of treatment with the active drug. In only one case there was heartburn and this was corrected with alkalines. In one other case an urticarial rash appeared, but disappeared spontaneously when the drug was temporarily stopped and did not reappear when it was administered again. During the trial no evidence of renal, hepatic or hematological malfunctions were observed. However, a slight tendency towards an increase in the GOT, GPT and LDH was observed, which was not statistically significant. The drug tested may be very useful in the treatment of type IV hyperlipoproteinemia, especially in those forms in which an increase in thromboembolic risk is suspected, either associated with, or secondary to, the actual atherosclerotic disease.

Evolution of spirographic patterns in pulmonary bilaterally denervated dogs.

One stage total bilateral pulmonary denervation produced in a group of 23 dogs an increase breathing frequency, an increase in the amplitude of respiration and a characteristic morphology of the spirographic pattern. Later in the evolution, these alterations returned to normal with the exeption of the amplitude of respiration which remained increased. This normalization was not accompanied by the reappearance of the Hering-Breuer reflux. Administration of an aerosol of acetylcholine after normalization of the spirographic pattern produced a temporary reappearance of the immediate postdenervation spirographic pattern. We postulate that in denervated lung a nervous plexus localized in the bronchi not related to the vagus might assume an important role in the regulation of respiration. One cannot exclude, however, the possibility that the reappearance of postdenervation pattern is due to stimulation of airways vagal receptors located in areas proximal to the level of the nervous section.