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T Fujiwara

Publications and source records attributed to T Fujiwara.

At least 1,081 records · Page 60Linked to original sources
PubMed1987

Metabolism of nilvadipine, a new dihydropyridine calcium antagonist, in rats and dogs.

1. The metabolic profiles of nilvadipine in the excreta of male rats and dogs were studied after i.v. and oral dosing. Six types of metabolites were isolated and identified from the urine of male rats and dogs or bile of rats. 2. Several metabolites were detected in the urine (12) and bile (17) of rats by two-dimensional t.l.c., after dosing with 14C-nilvadipine. The metabolic profiles in the excreta of rats and dogs were qualitatively similar but quantitative differences were observed. 3. The main metabolites were products of (i) oxidation of the 1,4-dihydropyridine ring to the corresponding pyridine, (ii) hydrolysis of the 5-isopropyl ester or 3-methyl ester group to carboxylic acid, and/or (iii) hydroxylation of the 6-methyl group or methyl group of the isopropyl ester chain. 4. Minor metabolites were products of hydrolysis from the 5-isopropyl ester to the carboxylic acid having a dihydropyridine ring, or reduction of the 3-nitro group of the phenyl moiety having a pyridine ring.

Animals↗
PubMed1987

Absorption, distribution and excretion of nilvadipine, a new dihydropyridine calcium antagonist, in rats and dogs.

1. The absorption, distribution and excretion of nilvadipine have been studied in male rats and dogs after an i.v. (1 mg/kg for rats, 0.1 mg/kg for dogs) and oral dose (10 mg/kg for rats, 1 mg/kg for dogs) of 14C-nilvadipine. 2. Nilvadipine was rapidly and almost completely absorbed after oral dosing in both species; oral bioavailability was 4.3% in rats and 37.0% in dogs due to extensive first-pass metabolism. The ratios of unchanged drug to radioactivity in plasma after oral dosing were 0.4-3.5% in rats and 10.4-22.6% in dogs. The half-lives of radioactivity in plasma after i.v. and oral dosing were similar, i.e. 8-10 h in rats, estimated from 2 to 24 h after dosing and 1.5 d in dogs, estimated from 1 to 3 d. In contrast, plasma concentrations of unchanged drug after i.v. dosing declined biexponentially with terminal phase half-lives of 1.2 h in rats and 4.4 h in dogs. 3. After i.v. dosing to rats, radioactivity was rapidly distributed to various tissues, and maintained in high concentrations in the liver and kidneys. In contrast, after oral dosing to rats, radioactivity was distributed mainly in liver and kidneys. 4. With both routes of dosing, urinary excretion of radioactivity was 21-24% dose in rats and 56-61% in dogs, mainly in 24 h. After i.v. dosing to bile duct-cannulated rats, 75% of the radioactive dose was excreted in the bile. Only traces of unchanged drug were excreted in urine and bile.

Animals↗
PubMed1987

Quantitative analysis of myocardial infarction in (NZW x BXSB)F1 hybrid mice with systemic lupus erythematosus and small coronary artery disease.

Male (NZW x BXSB)F1 mice ([W x B]F1) were used as a model for small coronary artery disease. The mortality rate for 162 mice was 0% at 12 weeks and 37% at 24 weeks. The incidence of myocardial infarction (MI) was 0% at 12 weeks, 22% at 16 weeks, 39% at 20 weeks, and 53% at 24 weeks. In 29 of the 35 (W x B)F1 male mice with MI, small multiple infarctions were noted in the right ventricular free wall and anterior, lateral, posterior, and septal ventricular walls. In 25 of the 29 hearts with multiple infarcts, the infarcts in the same heart were at the same histologic stage. Twenty-one of these hearts showed only replacement fibrosis, and 4 hearts showed only granulation. The remaining 4 hearts with multiple infarcts exhibited coagulation necrosis plus fibrosis or granulation. Quantitative analysis of the infarct size revealed that in the 35 (W x B)F1 males with MI, the relative area of MI (%MI) was significantly larger in the right ventricular free wall (6.7% +/- 8.4%) than in the ventricular septum (1.9% +/- 2.4%) or in the left ventricular free wall (2.1% +/- 2.5%). The %MI was greatest in the right third (3.6% +/- 5.4%) of the ventricular septum and in the outer third (2.9% +/- 3.3%) of the left ventricular free wall. The %MI did not increase with age. In 11 of the 35 (W x B)F1 mice, 27 intramural small arteries showed marked obliterative lesions. Most of them were in the right ventricular free wall, the right third of the ventricular septum, or the outer third of the left ventricular free wall. There was no evidence of stenosis in the extracardiac major coronary arteries. In addition, the infarct showed a whirlpool-like configuration, and x-ray photographs revealed that the small intramural coronary arteries had a whirlpool-like configuration. It is concluded that in (W x B)F1 males multiple small infarcts appear at the same time due to small coronary artery disease. The whirlpool configuration of the infarct reflects the special anatomy of the intramural coronary arteries in the mice.

Animals↗
PubMed1987

[Clinical features and significance of hypertrophic cardiomyopathy with atrial fibrillation].

To elucidate the clinical features of hypertrophic cardiomyopathy (HCM) with atrial fibrillation (Af), the complications and prognosis of 18 patients with HCM complicated by Af (Af group) were compared with those of 20 patients without Af (non-Af group). The Af group was categorized depending on duration as 1. Af group I (four patients) with persistent Af at diagnosis, 2. Af group II (10 patients) with transient Af of more than five hours' duration, and 3. Af group III (four patients) with Af less than five hours' duration. The results were as follows: 1. During the follow-up period, among the 18 patients in the Af group, five including four patients in the Af group I, developed arterial embolism, 10 developed congestive heart failure, and three died suddenly. The patients in the non-Af group had excellent courses without serious complications. 2. Electrical cardioversion was performed in six patients in the Af group II, and sinus rhythm was restored in all of them, resulting in improved clinical courses. Thus, no complications developed in four patients whose sinus rhythm was maintained and whose clinical courses were favorable. 3. The P-terminal force in V1 prior to onset of Af in the Af groups II and III, left atrial dimension, and the cardiothoracic ratio in the Af group, were significantly greater than that of the non-Af group (p less than 0.01, p less than 0.05, p less than 0.05, respectively). In conclusion, HCM associated with Af has a poor prognosis, with severe complications such as heart failure, arterial embolism and sudden death. Cardioversion may be an effective method of choice of intervention in patients with recently-developed Af. P-terminal force in V1, left atrial dimension, and cardiothoracic ratio are regarded important factors in the development of Af.

Adult↗
PubMed1987

Plasma levels of (+)- and (-)-nilvadipine after oral dosing with racemic (+)-nilvadipine in man.

The plasma levels of (+)- and (-)-nilvadipine 1 h after an oral dose of racemic (+)-nilvadipine 4 mg in sixteen healthy volunteers were studied to find the extent of variation between (+)- and (-)-nilvadipine plasma levels. Additionally the pharmacokinetic profiles of the enantiomers in the plasma up to 12 h after dosing were examined in three subjects. The plasma levels of the (+)- and (-)-nilvadipine in the three subjects peaked at 0.5-1 h, and the maximum concentration and the area under the plasma concentration-time curve of the more potent (+)-enantiomer were 2.38-3.18 and 2.27-3.10 times, respectively, higher than those of its optical antipode. The half-lives of the enantiomers were mostly similar. In the sixteen subjects, the ratio between (+)- and (-)-nilvadipine levels 1 h after dosing with racemic (+)-nilvadipine were from 1.77 to 3.65.

Administration, Oral↗