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PubMed1982

[Pharmacokinetic studies with 3H-labelled synthetic antifibrinolytics].

In rabbits and rats pharmacokinetic studies on the anti-fibrinolytics 4-aminomethylbenzoic acid (PAMBA), trans-4-aminomethylcyclohexane-1-carboxylic acid (AMCA), and epsilon-aminocaproic acid (EACA) were carried out using the tritium labelled compounds. Following i. v. administration of PAMBA and EACA in rabbits a two-phasic plasma level and following AMCA a three-phasic plasma level was found within 7 h. The rate constants beta of 0.34 h-1, 0.44 h-1, and 1.08 h-1 for EACA, PAMBA, and AMCA, respectively, indicate a more rapid elimination of AMCA. Accordingly, the AUC-values for AMCA are considerably smaller than those for EACA and PAMBA after both i. v. and p. o. administration.

4-Aminobenzoic Acid↗
PubMed1982

Bentiromide:xylose test in healthy cats.

The N-benzoyl-L-tyrosyl-p-aminobenzoic acid (bentiromide):xylose test for simultaneous evaluation of pancreatic exocrine function and intestinal absorptive function was studied in 8 clinically healthy cats. Plasma p-aminobenzoic acid (PABA) and xylose concentrations were determined before, and at 30, 60, 90, 120, 150, and 180 minutes after, a solution of bentiromide (1 g/100 ml) and D-xylose (10 g/100 ml) was given orally at a dosage of 5 ml/kg of body weight. The peak plasma concentrations for PABA occurred between 60 and 120 minutes, with highest mean value at 90 minutes (7.5 +/- 3.2 micrograms/ml), and for xylose between 30 and 120 minutes, with the highest mean value at 60 minutes (42.6 +/- 17.8 mg/dl). Large SD in plasma PABA and xylose concentrations indicated marked individual variation between healthy cats. It was concluded that (i) large variations between clinically healthy cats may limit the diagnostic usefulness of the bentiromide:xylose test in the cat, and (ii) guidelines for interpretation of plasma PABA and xylose concentrations reported previously for clinically healthy dogs could not be applied to cats because values were lower in cats.

4-Aminobenzoic Acid↗
PubMedDate not supplied

Use of Ac-L-Tyr-PAB for estimating the activity of chymotrypsin in rats.

Pancreatic secretion in rats was assessed by measuring the amounts of p-aminobenzoic acid (PABH) excreted in urine after oral administration of Ac-L-Tyr-PAB, and by determination of enzyme activity in pancreas and faeces. 3 groups of 7 rats were kept on diets with casein as the main source of nitrogen without (control K0) or with two levels of trypsin inhibitor (K1 and K2). Two other groups were fed diets with 40 and 80% of casein substituted by raw soya bean protein and having trypsin inhibitor contents equivalent to those in diets K1 and K2. Urinary excretion of PABH ranged from 99 to 105% of intake and were not different between control and experimental rats. The weight of pancreas and pancreatic activities of trypsin and chymotrypsin in all experimental rats were higher than in controls. The activity of chymotrypsin in the faeces of rats of groups K1 and K2 was greater than in K0 while in groups S1 and S2 it was about five times that in groups K1 and K2. Generally, it was greater on diets with more trypsin inhibitor. The activity of trypsin in the faeces of rats K0, K1 and S1 was several times less than in K2 and S2. It has been concluded that measurement of trypsin and chymotrypsin in faeces allows to estimate differences in the secretion of pancreatic enzymes.

4-Aminobenzoic Acid↗
PubMed1982

[Clinical trial of K-247].

The clinical trial of K-247, an anticancer drug showing antitumor effect by new mechanism of action, was performed in a total of 22 patients with a variety of advanced cancers, consisting of 10 cases administered singly and 12 cases combined with other anticancer agents. All patients were treated three or four times every day with oral administration of K-247 (600-800 mg/day). Including one patient receiving a high dosage (over 200 g totally) of K-247, in all cases, no appreciable side effect causing suspension of the administration was recognized. In combination therapies with other anticancer drugs there was rather found a tendency to rescue WBC from decrease. As a clinical result, although all cases tested were insusceptible to prior chemotherapy with various anticancer drugs, one case, which has received palliative operation for rectal cancer accompanied with pelvic infiltration, was experienced after administration of K-247 only, in which the destructive lesion of left sacral on X-ray photograph was restored to almost normal condition and the patient's complaints such as severe pain in the lower legs and difficulty in walking were completely disappeared.

4-Aminobenzoic Acid↗
PubMed1982

[Antitumor effects of p-aminobenzoic acid-N-xyloside Na--effects of single administration and combination with radiotherapy].

Therapeutic effect of p-aminobenzoic acid-N-xyloside Na (K-247) were studied. Eleven patients with a variety of solid tumors were treated with K-247 alone. K-247 was given orally 800mg daily for 4 weeks. As for side effect of the drug, only mild gastritis was observed in a few patients. Partial response (over 25% reduction of tumor size) with a median duration of two months was observed in 3 patients. These cases were metastatic tumor of lung from the carcinoma of thyroid, metastatic tumors of lung from the carcinoma of kidney, and mediastinal tumor. In eight patients the response was classified as no change and in one patient there was progressive disease. Thus K-247 has some therapeutic activity in patients with solid tumor. Combination therapy of irradiation and administration of K-247 were also studied. In twelve patients received the combination therapy, partial response was observed in 7 patients with complete response in 3 patients. In some patients it seems that the effect of irradiation was enhanced by K-247 administration. To confirm this observation, randomized controlled trial is required.

4-Aminobenzoic Acid↗
PubMed1982

[Immunological study of the actions of auxiliary antitumor agents--effects on lymphocyte transformation reaction and natural cytotoxicity activity in nude mice].

P-aminobenzoic acid-N-xyloside (K-247) and dimethyl-2- (tetrahydro-2-furanyl) ethylsulfonium-p-toluene sulfonate (GT-101) were tested their in vivo effects on both mitogen-induced lymphoproliferative reactions and natural cell-mediated cytotoxicities in BALB/c nude mice (homozygous and heterozygous) spleen lymphocytes. The animals were injected i.p. either 400 mg/kg of K-247 or 5 mg/kg of GT-101 (for 7 days consecutively). GT-101 caused a positive increase in lymphoproliferations by PHA and SPA, while the administration of K-247 had no effect on PHA-and SPA-induced lymphoproliferations. Furthermore, in a 12-hour 51Cr release assay, both drugs had no effect on the natural cell-mediated cytotoxicity against YAC-1 cells.

4-Aminobenzoic Acid↗
PubMed1982

[Clinical evaluation of anticancer therapy combined with p-aminobenzoic acid-N-xyloside].

Paraaminobenzoic acid-N-xyloside (K-247) is a new antitumor drug, which has no direct effect on immunologic status. Clinical trial of K-247 was performed in 8 patients with for advanced or recurred gastrointestinal cancer, who had short life expectancy. Oral administration of K-247, 600 to 900 mg/day, was carried out in combination with antitumor treatments using MMC, FT-207, 5-FU, PSK or irradiation. No toxic symptoms were observed in all patients. Of the 8 patients studied, one showed an encouraging response, while the remaining 7 patients were too far advanced to respond to these treatments.

4-Aminobenzoic Acid↗
PubMed1982

Antiatherogenic activity of cetaben sodium, sodium p-(hexadecylamino) benzoate, in the aortae of hypercholesteremic rabbits subjected to aortic endothelial cell desquamation.

The effects of sodium p-(hexadecylamino)benzoate [cetaben sodium] on plasma sterol concentrations, aortic sterol deposition and the incidence of atherosclerotic lesions in cholesterol-fed rabbits subjected to aortic deendothelialization with a balloon catheter have been studied. At a dose of 113 mg/kg/day, cetaben sodium decreased plasma cholesterol and the accumulation of aortic sterol and appeared to decrease the incidence of gross atherosclerotic lesions. At a dose of 27 mg/kg/day, no hypocholesteremic activity was observed, but cetaben sodium decreased both aortic sterol deposition and lesion development in the abdominal segment of the aorta. The decreases in total aortic sterol content observed in the drug-treated rabbits were shown to have resulted from a reduction in esterified rather than free sterol. When tested in vitro, cetaben sodium effectively inhibited (KI = 7.4 x 10(-5) M) the esterification of cholesterol catalyzed by a crude preparation of fatty acyl CoA:cholesterol acyl transferase isolated from cholesterol-fed rabbit aortae. These observations suggest that cetaben sodium possesses antiatherosclerotic activity and that this activity may result from direct actions on the aortic wall, in addition to vascular effects secondary to hypocholesteremic activity.

4-Aminobenzoic Acid↗
PubMed1981

Clinical study of exocrine pancreatic function test by oral administration by N-benzoyl-L-tyrosyl-p-aminobenzoic acid.

The clinical usefulness of a simple exocrine pancreatic function diagnostic test (PFT) was examined by the oral administration of 500 mg of N-benzoyl-L-tyrosyl-p-aminobenzoic acid. Recovery of p-aminobenzoic acid (PABA) in the urine was significantly lower in patients with calcifying chronic pancreatitis (58.6%) and noncalcifying chronic pancreatitis (68.6%) than in healthy normal subjects (81.0%; p less than 0.001 and p less than 0.05, respectively). Abnormally low values were demonstrated in 15 out of 19 (78.9%) chronic pancreatitis cases. In comparing the PFT with the pancreozymin secretin test, a good correlation (P less than 0.001) with maximum bicarbonate concentration was detected. In cases which were abnormal with respect to the PFT, the recovery rate of PABA was increased by the administration of antacids or digestive enzyme preparations (average increase of 24.1 or 29.8%, respectively). These results suggest that this test is also useful for the evaluation of therapeutic effects in patients with pancreatic diseases.

4-Aminobenzoic Acid↗
PubMed1980

New strategies in the development of anti-atherosclerotic drugs.

The results of several recently completed trials of cardiovascular prevention, by the use of hypolipidemic or anti-platelet compounds, have suggested that new strategies be followed for the development of anti-atherosclerotic drugs. The final outcome of preventive studies with hypolipidemic compounds is markedly influenced by the significance of the achieve hypolipidemia, as well as by the side-effects, some which, i.e. lithogenicity, may be related to the drugs' mechanism of action. Significant differences may, moreover, exist between the findings in animal models and in humans, particularly by clofibrate and related compounds. The evaluation of drugs active on lipoprotein biosynthesis in the gut (metformin), potent enzyme inhibitors (compactin) and with chelating activity (cetaben), is awaited with interest. In the field of drugs affected platelets, a selective sensitivity for the major compounds in different vascular areas has been observed. Aspirin appears to be mostly effective in cerebro-vascular prevention. Agents affecting the thrombin-platelet coagulation interaction, i.e. GYKI 14,451, may offer an interesting opportunity for testing the importance of this pathway in clinical thrombosis.

4-Aminobenzoic Acid↗
PubMedDate not supplied

[Study of the histaminergic mechanisms of the action of malaben].

In rabbits (intact and with experimental myocardial infarction) histamine metabolism (histamine content and diaminoxidase activity) following introduction of malaben was studied. In intact animals the ability of malaben to reduce the blood histamine level and to activate diaminoxidase was discovered. Administration of malaben in experimental myocardial infarction promotes a quicker normalization of the disturbed metabolism of histamine.

4-Aminobenzoic Acid↗
PubMedDate not supplied

[Protease inhibitors as immunomodulators in experimental acute pancreatitis and staphylococcal infection].

The influence of protease-inhibiting preparations on the development of humoral immune response in diseases involving the development of secondary immunodeficiency (experimentally induced acute pancreatitis and staphylococcal infection) has been studied. Five injections of contrycal and epsilon-aminocaproic acid (epsilon-ACA), starting from day 1 after the induction of acute pancreatitis, normalized the immune response induced by sheep red blood cells 24 hours after operation. In staphylococcal infection protease-inhibiting preparations (contrycal, epsilon-ACA, Amben) produced a protective effect, increasing the survival rate and the mean survival time of the animals infected with staphylococci.

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