Biomedical subjects

Y Takiguchi

Publications and source records attributed to Y Takiguchi.

150 records · Page 9Linked to original sources

PubMedDate not supplied

Phase I study of cefixime, a new oral cephalosporin.

The tolerance to and pharmacokinetics of cefixime, a new oral cephalosporin, were evaluated in healthy volunteers given the drug in single doses of 50, 100 and 200 mg and repeated doses of 200 mg bid for 14 days. In the repeated-dose study, there were mild and transient subjective symptoms such as soft stools, diarrhea, and anorexia, which disappeared without additional treatment during the dosing period. Slight increases in eosinophil and serum amylase levels were also observed. The serum concentrations of cefixime peaked at 0.71, 1.17, and 2.08 micrograms/mL on average, four to five hours after dosing with 50, 100, and 200 mg, respectively, and the half-lives were 2.54, 2.38, and 2.29 hours. Serum concentrations and urinary recoveries after dosing with 100 mg were little affected by food ingestion. There was no evidence of cefixime accumulation in the body by repeated dosing since mean serum concentrations and urinary recoveries were almost the same on the first, third, seventh, and 14th days of dosing.

Adult↗

PubMedDate not supplied

Effects of nicardipine, a dihydropyridine calcium antagonist, on regional myocardial blood flow, myocardial oxygen tension, and electrical abnormalities during acute coronary artery occlusion in dogs.

Effects of nicardipine, a dihydropyridine calcium antagonist, on regional myocardial blood flow (RMBF), myocardial oxygen tension (PO2), and excitation and conduction abnormalities during the occlusion of the left anterior descending coronary artery (LAD) were examined in anesthetized dogs, and compared with those of nifedipine and dipyridamole. RMBF was calculated from the H2 gas clearance curves, and PO2 was measured using a membrane-coated Pt wire. Excitation and conduction abnormalities during the LAD occlusion were represented in terms of the degree of ST-T alternans (STTA), TQ depression, and conduction delay, which appeared in epicardial electrograms. Nicardipine and nifedipine in a dose of 10 micrograms/kg increased RMBF and PO2 levels in nonischemic and mildly ischemic tissues, but not in severely ischemic tissues. Nicardipine in a dose of 100 micrograms/kg and nifedipine in a dose of 10 micrograms/kg attenuated the degree of STTA, TQ depression, and conduction delay observed in severely ischemic tissues. In mildly ischemic tissues where only TQ depression was observed without STTA, nicardipine in a dose of 30 micrograms/kg attenuated TQ depression. Dipyridamole in a dose of 1 mg/kg produced only a slight attenuation of STTA and conduction delay. These results suggest that the beneficial effects of nicardipine as well as of nifedipine on myocardial ischemia are due to the increase in the myocardial PO2 levels caused by the increased RMBF and also to direct protecting effects on ischemic myocardial cells. In the severely ischemic tissues, the latter is a main effect of the drugs. In increasing the PO2 level, nicardipine was similarly potent as nifedipine, but in the direct effect, nicardipine was less potent, and dipyridamole was almost ineffective.

Animals↗

PubMedDate not supplied

UV-dependent quinolone-induced human erythrocyte membrane lipid peroxidation: studies on the phototoxicity of Y-26611, a new quinolone derivative.

Quinolone antibacterial drugs are widely used as oral therapeutic agents. However, in some patients they cause ultraviolet (UV)-dependent dermatitis. Using lipid peroxidation as an index of phototoxicity, we studied the effects of a new quinolone derivative, Y-26611 together with ofloxacin, sparofloxicin and lomefloxacin on washed human erythrocyte suspensions. Irradiation of erythrocytes with UV-A or UV-B for 60 min. in the presence of Y-26611 (30-600 micrograms/ml) strong dose dependent lipid peroxidation, up to 17.01 nmoles/ml was induced. Under identical conditions, lipid peroxidation induced by up to 600 micrograms/ml ofloxacin, sparofloxacin or lomefloxacin were 0.94, 3.36 and 2.98 nmoles/ml respectively. The lipid peroxidation was entirely dependent on both UV as well as the drug. The lipid peroxidation responses to drug+UV could completely be inhibited by sodium azide (hydroxyl radical, HO. and single oxygen, 1O2 scavenger) or by phenyl N-tert-butylnitrone (PBN, HO. and superoxide anion radical, O2- scavenger). It is likely that reactive oxygen species generated by interaction between UV-sensitized drug molecules and oxygen molecules mediate erythrocyte membrane lipid peroxidation. The method used in this study is rapid and convenient for screening drugs for UV-dependent cytotoxicity.

4-Quinolones↗

PubMedDate not supplied

Acute effects of griseofulvin on the pharmacokinetics and pharmacodynamics of warfarin in rats.

It has been reported that prothrombin time (PT), which is prolonged by warfarin, is reduced when patients on warfarin also take griseofulvin repeatedly. We investigated the cause of the drug interaction and the initial effects of griseofulvin on warfarin pharmacokinetics. Total cytochrome P-450, and the activities of aminopyrine N-demethylase, aniline p-hydroxylase and 7-ethoxycoumarin O-deethylase, after repeated administration of griseofulvin (100 mg/kg orally daily for 5 days) were examined. Acute effects of single doses of griseofulvin (100 mg/kg) on coagulation activity (prothrombin time) and warfarin pharmacokinetics after administration of warfarin were also studied. Repeated administration of griseofulvin induced warfarin-metabolizing enzymes. In contrast, a single administration of griseofulvin increased prothrombin time and serum warfarin concentrations. The activity of a warfarin-metabolizing enzyme (7-ethoxycoumarin O-deethylase) was reduced when griseofulvin was added to rat liver microsomes. The results suggest that reduced warfarin action after repeated administration of griseofulvin may be due to induction of warfarin-metabolizing enzymes, but that there is also an initial increase in warfarin action.

Animals↗

PubMedDate not supplied

Augmented responsiveness to sympathetic nerve stimulation of isolated vas deferens of diabetic rats.

The responsiveness to nerve stimulation in the prostatic end of the rat vas deferens and the influence thereupon of streptozotocin-induced diabetes were examined. The rat vas deferens showed a biphasic contractile response to field stimulation: a rapid twitch contraction followed by a slower tonic contraction. Diabetic rats, at 8 and 12 weeks after induction of diabetes, showed a significant increase in the tonic response when compared with age-matched control rats. The twitch response was slightly increased in 12 week diabetic rats at low frequencies of stimulation. Treatment with insulin reversed the augmented response to nerve stimulation found in diabetic rats. The tonic phase in control rats was inhibited by prazosin (73.5%), and by alpha,beta-methylene ATP (34.6%). In diabetic rats at 12 weeks, about 30% of the tonic response was inhibited by prazosin; in the presence of prazosin, the response was still significantly augmented in comparison with that in control rats. In contrast, the tonic response in the presence of alpha,beta-methylene ATP was the same in diabetic and control rats. These results indicate that diabetes induces an increase in the purinergic component of the response to sympathetic nerve stimulation of the rat vas deferens.

Adenosine Triphosphate↗

PubMedDate not supplied

Alterations of cardiac adrenoceptors and calcium channels subsequent to production of aortic insufficiency in rats.

Aortic insufficiency (AI) was produced in rats by puncturing one of the aortic valves with a plastic rod inserted from the right carotid artery, and the subsequent changes in alpha- and beta-adrenoceptors and Ca2+ channels were investigated by means of radioligand binding assays. The positive inotropic effects of methoxamine (Met), isoproterenol (Iso) and Ca2+ were also examined in isolated left papillary muscles. The ratio of the whole heart weight to body weight in AI rats increased significantly as compared with sham-operated rats from 1 till 8 weeks after operation, showing that a cardiac hypertrophy had occurred due to the volume overload. Maximum binding sites (Bmax) for 3H-prazosin in cardiac ventricular muscles of AI rats significantly increased at 4 weeks and returned to the control level at 8 weeks when the AI was still patent. Bmax for 3H-dihydroalprenolol (3H-DHA) of AI rats significantly increased at 2 and 4 weeks and returned to the control level at 8 weeks. Bmax for 3H-nitrendipine binding of AI rats significantly decreased at 2 weeks and returned to the control level at 4 weeks. Affinities for these bindings, as expressed by values of dissociation constants, showed no significant changes. The sensitivities of papillary muscles to Met and Iso were significantly increased in AI rats at 4 weeks. Plasma immunoreactive alpha-atrial natriuretic polypeptide (alpha-ANP) concentration of AI rats tended to increase from 1 till 3 weeks and returned to the control level at 4 weeks but these changes were not significant. We conclude that the synthesis of new adrenoceptors keeps pace with the hypertrophic process and may even overshoot during a short period.

Animals↗