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T Oka

Publications and source records attributed to T Oka.

At least 1,027 records · Page 57Linked to original sources
PubMed1988

Determination of the calcium antagonist benidipine hydrochloride in plasma by sensitive radioimmunoassay.

A sensitive radioimmunoassay of the 1,4-dihydropyridine calcium channel blocker (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) has been developed. Antiserum against KW-3049 was produced in rabbits by immunization with an immunogen prepared by conjugating a derivative of KW-3049 to bovine serum albumin. This antiserum was found to specifically bind to [3H]-KW 3049, while the recognition to [3H]-nitrendipine, another well-known dihydropyridine calcium channel blocker, was less pronounced. With the antiserum, [3H]-KW-3049 and dextran coated charcoal, this radioimmunoassay could detect 39 approximately equal to 500 pg/tube of KW-3049 in a buffer system, and 156 to 5000 pg/ml of KW-3049 in plasma by using 0.5 ml of the plasma which was pretreated with MeOH for deproteinization and extracted with diethyl ether under alkaline condition. To assess the specificity of the radioimmunoassay, the inhibition of [3H]-KW-3049 binding to the antiserum by the presumable metabolites was examined. Though three of these presumable metabolites could slightly inhibit the binding of [3H]-KW-3049, they were not detected in rat and dog plasma at 0.5 h after oral administration of KW-3049. Plasma levels of KW-3049 in rats receiving a single oral dose (1 mg/kg) determined by the radioimmunoassay show good agreement with those obtained by gas chromotography.

Animals↗
PubMed1988

Absorption, distribution and excretion after oral administration of 14C-benidipine hydrochloride in rats and dogs.

(+/-)-(R*)-2,6-Dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5- dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) has been developed as antihypertensive and antianginal agent. The absorption, distribution and excretion were investigated after single oral administration of 14C-labeled KW-3049 using Wistar rats and beagle dogs. The results were summarized as follows: 1. After oral administration of 14C-KW-3049 to rats, the plasma radioactivity reached the maximum at 0.5 h, showed the second peak at 4 h and decreased biphasically with the biological half-lives of about 6 h and 38 h. 2. After oral administration of 14C-KW-3049 to dogs, the plasma radioactivity reached the maximum at 1 h and decreased biphasically with the biological half-lives of about 2 h and 25 h. 3. After oral administration to rats and dogs, the excretion of the radioactivity in feces and urine during 72 h (rats) and 96 h (dogs) were 74% and 19%, 66% and 25%, respectively. The radioactivity excreted in the bile was 34% during 48 h and was followed by partial reabsorption from the gastrointestinal tract. 4. High radioactivities were observed in the digestive organs, mesenteric lymphnodes, liver, pancreas, urinary bladder, fat tissue, kidney and spleen after oral administration to rats.

Administration, Oral↗
PubMed1988

Absorption, distribution and excretion of 14C-benidipine hydrochloride after repeated administration to rats.

The absorption, distribution and excretion of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) were studied after repeated doses to rats. The results were summarized as follows: 1. After oral repeated administration once a day for 3 weeks, the radioactivities in blood and tissues increased up to the 14th day, and thereafter they tended to show the steady state. 2. The radioactivity in the tissues at 1 h after last dosing was compared with that at 1 h after single administration. Both tissue distribution patterns were not markedly different, but the concentrations in the liver, testicles, skin and descending aorta significantly increased, showing approximately the 2-fold radioactivities. 3. The radioactivities were excreted in the urine (6%) and feces (88%). The excretion of radioactivity in urine and feces did not change markedly during the repeated administration period.

Administration, Oral↗
PubMed1988

Pharmacokinetic study of benidipine hydrochloride in rats and dogs.

(+/-) - (R*) - 2,6-Dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine - 3, 5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) is presently under development as an anti-hypertensive and antianginal agent. A pharmacokinetic study in rat and dog after oral and intravenous administrations revealed that KW-3049 was rapidly absorbed from the gastrointestinal tract, distributed into tissues moderately and comparatively quickly eliminated. After oral administration, non-linearity of bioavailability with increment of doses was observed in both rat and dog. Female and male rats showed similar drug disposition after intravenous administration. Oxidation product of KW-3049 dihydropyridine ring was also measured in some plasma samples. The concentration rates of its pyridine metabolite accounted for 0 to 30% and 0 to 23% of the combined concentration of KW-3049 plus the pyridine metabolite in rat and dog.

Administration, Oral↗
PubMed1988

Identification of benidipine hydrochloride metabolites in rats and dogs.

A study of the metabolism of [14C]-(+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)- 1,4-dihydropyridine-3, 5- dicarboxylic acid (R*)-1-benzyl-3-piperdidinyl ester, methyl ester hydrochloride (14C-benidipine hydrochloride, 14C-KW-3049) revealed as major metabolic pathways oxidative N-dealkylation, hydrolysis of the ester moiety, dehydrogenation of the 1,4-dihydropyridine ring, hydroxylation of the methyl group and decarboxylation in rat and dog. Rat and dog showed similar metabolic pathways, but some quantitative differences were found between rat and dog.

Animals↗
PubMed1988

Benidipine hydrochloride--a new calcium-channel blocker of the dihydropyridine type. Pharmacokinetics, pharmacodynamics, tolerance and dose finding in mild to moderate hypertension.

(+/-)-(R*)-2,6-Dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3, 5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) is a newly synthetized calcium-channel blocker of the dihydropyridine type. In a phase I study with increasing single doses a statistically significant increase of the heart rate in supine and upright position as well as statistically significant decrease of the blood pressure in upright position was observed in healthy volunteers 1.5-6 h after application of 24 mg of KW-3049. Subsequently, in a placebo-controlled comparison in healthy volunteers the pulse rate in supine position increased statistically significantly on day 1 from 61.0 b/min (placebo) after application of 2 x 8 mg of KW-3049 to 67.4 b/min. After application of 2 x 10 mg of nifedipine the supine pulse rate increased to 63.3 b/min. The difference from placebo was not significant. At days 2-5 the pulse rate in upright position was always increased vs. placebo 3 h after application of KW-3049 and 1 h after application of nifedipine. As already observed in preclinical data, the mild onset of action with KW-3049 was also confirmed in these clinical phase I studies. Drug-induced effects on ergometric and psychomotoric parameters in healthy volunteers were mild, as expected, and due to aliquote dosages of 2 x 8 mg of KW-3049 and 2 x 10 mg of nifedipine only slightly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

[Late occlusion at the anastomosis site of an extended polytetrafluoroethylene (E-PTFE) graft with small caliber].

Recently expanded polytetrafluoroethylene (E-PTFE) graft is often used in arterial bypass for atherosclerosis obliterans. In our series of 38 patients (48 legs) undergoing femoropopliteal bypass with E-PTFE graft of 6mm-caliber, a cumulative patency rate was 40.8% at 36 months after operation and a mean duration of patency was 26.3 months. To clarify the cause of occlusion, the diseased grafts were removed and histopathologically examined. Macroscopically, the E-PTFE graft was occluded by the intimal hyperplasia, so called pannus ingrowth from the recipient artery into the graft. The pannus formation of the graft was more remarkable in the distal than in the proximal site of anastomosis, suggesting the influence of blood flow on its formation. Microscopically, no endothelial cells were observed inside the E-PTFE graft except for the surface of pannus. Thus, less extension of endothelialization was thought to be a cause of late occlusion in E-PTFE grafts. Most desirable is the autologous saphenous vein for femoropopliteal bypass. However, when it is not available, E-PTFE graft with a larger caliber must be used in combination with postoperative anticoagulant therapy.

Arteriosclerosis Obliterans↗
PubMed1988

[Ceftriaxone in neonates and young infants; clinical efficacy, pharmacokinetic evaluation and effect on intestinal bacterial flora].

Twenty-two newborn and young infants, including 13 premature infants, were treated with ceftriaxone (CTRX) and the clinical efficacy and side effects were evaluated. Ages of the patients ranged from 0 to 106 days, and their body weights from 1.19 to 3.92 kg. Dose levels were 15 to 23 mg/kg every 12 to 24 hours for 2 to 13.5 days. Eighteen infants with sepsis and 1 infant with purulent coxitis were considered to have responded to the CTRX treatment. The results were excellent in 13 and good in 6 patients. The drug was well tolerated, although diarrhea occurred in 2 patients, eosinophilia in 6 patients, slightly elevated serum concentrations of transaminases in 2 patients and thrombocytosis in 1 among the 22 patients. The pharmacokinetic studies on CTRX were done in 8 patients including 3 premature infants. The ages ranged from 3 to 50 days, and body weight from 2.20 to 3.94 kg. Plasma concentrations 30 minutes after single 10 mg/kg intravenous bolus injection in two 4- to 5-day-old premature neonates were 48.4 and 50.0 micrograms/ml and those at 6 hours were 22.7 and 23.4 micrograms/ml, respectively. In 2 mature neonates, plasma levels were 42.2 and 39.1 micrograms/ml at 30 minutes and 23.4 and 26.6 micrograms/ml at 6 hours after single 20 mg/kg doses. In four 12- to 50-day-old patients, plasma concentrations ranged from 35.9 to 175.0 micrograms/ml at 30 minutes and from 21.9 to 32.8 micrograms/ml at 6 hours after multiple doses of 20 mg/kg intravenous bolus injection. The plasma half-lives of the drug ranged from 6.6 to 16.8 hours in these 8 patients. Excretion rates of this drug into urine within 12 hours were 21.4 to 63.4% in 7 patients. Urine concentrations of the drug in 34 samples collected at various times from the 7 patients ranged from 28.3 to 469.0 micrograms/ml. The cerebrospinal fluid level at 2 hours after a dose was 3.33 micrograms/ml on the 5th day of treatment in 1 patient with sepsis receiving 18 mg/kg of the drug every 12 hours. Its level at 3 hours after a dose was 6.07 micrograms/ml on the 6th day of treatment in another patient with aseptic meningitis receiving 20 mg/kg every 12 hours. The influence of CTRX on the fecal flora was studied in 3 patients receiving 20 mg/kg X 2/day. The characteristic pattern observed during the drug administration was the disappearance of Bifidobacterium and Enterobacteriaceae, the preservation of Streptococcus and Staphylococcus, and the increase in Candida.(ABSTRACT TRUNCATED AT 400 WORDS)

Birth Weight↗