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排序方式: 共有44条查询结果,搜索用时 15 毫秒
1.
Hiroyuki Yasui Kiyoshi Yamaoka Terumichi Nakagawa 《Journal of pharmacokinetics and pharmacodynamics》1995,23(2):183-203
A new hepatocellular diffusion model was developed to kinetically evaluate the hepatobiliary transport processes of drugs
in the perfusion system, based on the physiological structure of the liver. Since the equations describing the hepatocellular
diffusion phenomena were derived as image forms in the Laplace domain, the fast inverse Laplace transform (FILT) was adopted
to manipulate the image equations. Cefixime and cefpiramide were selected as model drugs. The concentrations in the perfusate
and the excreted amounts into the bile were simultaneously measured at appropriate intervals after the rapid administration
of each drug into the portal vein. The hepatocellular diffusion model was fitted to the biliary excretion profiles from rat
livers, by means of a nonlinear least squares program, MULTI(FILT). According to this model, the hepatobiliary transport process
of drug is kinetically separated into three steps, that is, the diffusion into and through the hepatocytes, the transfer from
the hepatocytes into the bile canaliculi, and the movement through the bile canaliculi to the outlet of bile duct. These steps
are characterized by the diffusion rate constant through hepatocytes (kdif), the permeability rate constant into the bile canaliculi (kbmc) and the transit time through the bile canaliculi to the outlet of bile duct (
), respectively. It was demonstrated that kdif of cefixime (0.023min1) was significantly smaller than that of cefpiramide (0.044 min1), while the differences in kbmc and
were not obvious between cefixime and cefpiramide. kbmc and
of both drugs were about 1.2 min1 and about 1.0 min, respectively. These parameters were correlated to the excretion ratio into the bile (Fbile) and the mean transit time from the sinusoid through the hepatocytes to the outlet of bile duct (
). 相似文献
2.
Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations 总被引:13,自引:0,他引:13
Kiyoshi Yamaoka Terumichi Nakagawa Toyozo Uno 《Journal of pharmacokinetics and pharmacodynamics》1978,6(2):165-175
According to linear pharmacokinetics, the time course of plasma concentration of a drug, Cp,is expressed by a sum of exponential functions, Cp=
i=1
n
ai
.This article describes a statistical technique to estimate the number of exponential terms, n,for the time course of drug by the application of Akaike's information criterion (AIC). Plasma concentrations of ethoxybenzamide, sulfisoxazole, bishydroxycoumarin, and diazepam measured following bolus intravenous injection were used as clinical examples for this method. Selection of models is compared between the AIC method and an Ftest method at significance levels of 5% and 1%. 相似文献
3.
Quetiapine treatment for behavioral and psychological symptoms in patients with senile dementia of Alzheimer type 总被引:5,自引:0,他引:5
Fujikawa T Takahashi T Kinoshita A Kajiyama H Kurata A Yamashita H Yamawaki S 《Neuropsychobiology》2004,49(4):201-204
The purpose of this study was to assess the effect of quetiapine in the treatment of behavioral and psychological symptoms of dementia (BPSD) in patients with senile dementia of Alzheimer type (SDAT). Sixteen SDAT patients with BPSD were recruited and quetiapine (25- 200 mg/day) was prescribed for 8 weeks. BPSD were evaluated with the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) and Cohen-Mansfield Agitation Inventory (CMAI) at week 0 (baseline) and week 8 (endpoint). The severity of the extrapyramidal symptoms was also assessed by the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) at baseline and endpoint. Significant improvements were seen in the CMAI total score and in the BEHAVE-AD subscales of delusions, activity disturbances, aggressiveness, diurnal rhythm disturbances and in the BEHAVE-AD overall severity. There was no significant difference between the baseline and endpoint in the DIEPSS score. These data indicate that quetiapine is effective in controlling BPSD with favorable adverse-event profiles. 相似文献
4.
Akimasa Shibukawa Yukihiro Kuroda Terumichi Nakagawa 《Journal of pharmaceutical and biomedical analysis》1999,18(6):4460
High-performance frontal analysis (HPFA) is a novel analytical method which enables simultaneous determination of total and unbound drug concentrations under drug–plasma protein binding condition. HPFA can be achieved using separation systems such as HPLC and CE. This paper deals with the principle and feature of HPFA method and its application to the stereoselective protein binding study. HPFA allows a simple analysis following direct sample injection, and does not suffer from undesirable drug adsorption on membrane nor leakage of bound drug through the membrane which are often encountered in conventional ultrafiltration and dialysis methods. HPFA can be easily incorporated into on-line HPLC system. By coupling HPFA with a chiral HPLC column, the unbound concentration of a racemic drug can be determined enantioselectively. The detection limit can be improved by coupling of HPFA with a preconcentration column. High-performance capillary electrophoresis/frontal analysis (HPCE/FA) enables to determine unbound concentrations enantioselectively with ultramicro injection volume, and is hence useful especially for the binding study of proteins which are scarce and difficult to obtain. 相似文献
5.
Yoshitaka Yano Kiyoshi Yamaoka Hiroyuki Yasui Terumichi Nakagawa 《Journal of pharmacokinetics and pharmacodynamics》1991,19(1):71-85
An arterial and venous blood (or plasma) concentration difference of drugs across the lung of rats was evaluated based on the recirculatory concept. The recirculatory system is given by the combination of the transfer functions for the pulmonary and the systemic circulations and is described by a Laplace-transformed equation, i.e., an image equation. For the manipulation of the image equations, the fast inverse Laplace transform (FILT) was adopted and MULTI(FILT) was used for the simultaneous curve fitting to estimate the pharmacokinetic parameters in the recirculatory model. Metoprolol as a test drug and cephalexin as a control drag were infused, respectively into the femoral vein for 30 min, and arterial and venous blood samples were collected simultaneously through the cannula at the femoral artery and at right atrium during and after the infusion. Exponential functions were assumed for the weight functions through both the pulmonary and systemic circulations. Results of the curve fitting showed that the single-pass extraction ratio through the pulmonary circulation (Ep)of meloprolol was about 0.2, whereas that of cephalexin was negligible. The mean transit times through the pulmonary circulation (¯tp
of metoprolol and cephalexin were both about 0.5 min, which is small. The singlepass extraction ratios through the systemic circulation (Es)of metoprolol and cephalexin were both about 0.1. and the mean transit times through the systemic circulation (¯ts
were 11.5 min and 8.2 min, respectively. 相似文献
6.
Iwamoto Y Morinobu S Takahashi T Yamawaki S 《Progress in neuro-psychopharmacology & biological psychiatry》2007,31(3):642-651
Rats subjected to single prolonged stress (SPS) show enhanced HPA negative feedback, exaggerated acoustic startle response, and enhanced contextual freezing 7 days after SPS, and accordingly, SPS is an animal model of PTSD. To elucidate the influence of contextual fear on gene expression in the hippocampus of SPS rats, we used cDNA microarray followed by real-time quantitative PCR analyses to compare the hippocampal gene expression profiles between rats that were or were not subjected to SPS during exposure to contextual fear. In the behavioral experiments, spontaneous locomotor activity was measured 7 days after SPS. Twenty-four hours after footshock conditioning (7 days after SPS), freezing behavior was measured during re-exposure to the chamber in which footshock was delivered. Based on the behavioral analysis, rats subjected to SPS exhibited a significant enhancement of contextual freezing compared to rats not subjected to SPS, without any changes in locomotor activity. Analyses using cDNA microarray and RT-PCR showed that the hippocampal levels of glycine transporter 1 (Gly-T1) and vesicle-associated membrane protein 2 (VAMP2) mRNA in rats subjected to SPS were significantly increased relative to sham-treated rats. Administration of SPS alone did not affect the expression of these 2 genes. These findings suggest that the upregulation of Gly-T1 and VAMP2 in the hippocampus may be, at least in part, involved in the enhanced susceptibility to contextual fear in rats subjected to SPS. 相似文献
7.
8.
Mitsuhiro Sumitani Tatsurou Mikawa Yosihiro Miki Keiko Nisida Yoshihiro Tochino Takao Kamimori Hiroshi Fujiwara Terumichi Fujikawa Fukumi Nakamura 《Nihon Kokyūki Gakkai zasshi》2005,43(7):427-431
A 16-year-old boy had eaten Chinese freshwater crabs soaked in liquor in October 2000, and the left pleural effusion was pointed out on chest X-ray films at a regular medical checkup at school in June 2002. Since his father and friends had suffered from Paragonimiasis Westermani and had been treated in January 2001, the patient agreed to immunoserological examination, and Paragonimiasis Westermani was diagnosed. After drainage of pleural effusion, the patient was treated with praziquantel for three days at a daily dosage of 75 mg/kg, but without effect. The patient received drainage of pleural effusion again, and was treated with praziquantel for 3 days at a daily dosage of 75 mg/kg in a series of three treatments at three week interval. After that, improvement of the disease was achieved. 相似文献
9.
Effect of paroxetine on enhanced contextual fear induced by single prolonged stress in rats 总被引:2,自引:0,他引:2
Rationale Single prolonged stress (SPS) is an animal model of posttraumatic stress disorder (PTSD) that can reproduce enhanced hypothalamo-pituitary-adrenal negative feedback.Objectives We examined whether SPS can produce an enhanced psychophysiological reactivity to laboratory stressors unrelated to trauma and whether paroxetine (PRX) can alleviate the enhanced anxiety and fear response in rats subjected to SPS. Furthermore, the effect of PRX on pain sensitivity was examined in rats with and without SPS.Methods Rats were subjected to SPS (restraint for 2 h, forced swim for 20 min, and ether anesthesia) and then kept undisturbed for 14 days. After that, contextual fear response was assessed. Twenty-four hours after foot shock conditioning, freezing behavior was measured during reexposure to the shock environment for 3 min. Pain sensitivity was assessed by the flinch–jump test. PRX (0.01, 0.03, or 0.1 mg/mL) was chronically administered orally in drinking water.Results Rats subjected to SPS showed a significant increase in contextual freezing compared to rats without SPS. Chronic administration of PRX at concentrations of 0.03 and 0.1 mg/mL (which produced serum concentrations similar to those that are clinically relevant) caused significant suppression of the enhanced contextual freezing. Acute administration of PRX at a dose producing clinically relevant serum concentrations did not affect the enhanced freezing.Conclusions Our results suggest that SPS can reproduce behavioral alteration similar to that observed in patients with PTSD, and this elevated fear response can be alleviated by the chronic administration of PRX at doses producing clinically relevant serum concentrations. 相似文献
10.
Shortening hospital stays has become a key focus in psychiatric care in recent years. However, patients with schizophrenia account for about 60% of inpatients in psychiatry departments in Japan. This study was designed to investigate the relationship between quality of life (QOL) and key indicators for long-term hospital stays among schizophrenia inpatients. A further aim was to elucidate the clinical determinants of QOL among long-stay inpatients. The study sample consisted of 217 inpatients with schizophrenia. Age, duration of illness, duration of hospitalization, years of education, body mass index, neurocognitive function, drug-induced extrapyramidal symptoms, involuntary movements, psychiatric symptoms, and dose equivalents of antipsychotics and anticholinergic agents were used as index factors. Pearson linear correlation and regression analyses were performed to examine the associations between QOL and the above-mentioned factors. Negative symptoms, psychological discomfort, and resistance as rated on the Brief Psychiatric Rating Scale (BPRS) were correlated with all subscale scores of the Japanese version of the Schizophrenia Quality of Life Scale (JSQLS). Stepwise regression showed that negative symptoms, psychological discomfort, and resistance predicted the dysfunction of psycho-social activity score and the dysfunction of motivation and energy score on the JSQLS. This study shows that active treatment for negative symptoms, psychological discomfort, and resistance should be recommended to improve QOL among inpatients with schizophrenia. 相似文献