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11.
E Nakashima K Yokogawa F Ichimura T Hashimoto T Yamana A Tsuji 《Journal of pharmaceutical sciences》1987,76(1):10-13
The effects of fasting on the pharmacokinetics of biperiden in rats were examined. Total clearance of biperiden was greater than 90% ascribable to hepatic clearance and was essentially blood-flow dependent. The number of compartments in the preferred pharmacokinetic model of biperiden changed from three (for normal rats) to two (for fasted rats). The smaller mean residence time (MRT) values found for fasted rats were attributable to decreases in distribution volume. Biperiden showed much higher lipophilicity than haloperidol, thiopental, and hexobarbital, and its tissue-to-plasma partition coefficient in adipose tissue was 20-fold higher than that in muscle. The influence of changes in volumes of adipose tissue and muscle on distribution volume (Vdss/BW) was evaluated from tissue-to-plasma partition coefficients. The value of Vdss/BW was predicted to decrease with decrease of adipose tissue, and to increase with decrease of muscle tissue. These results suggest that the observed decrease of Vdss/BW in fasted rats reflects reduced capacity to trap biperiden in the body, especially in adipose tissue. Possible clinical implications of these results are discussed. 相似文献
12.
Phase I study of E1040, a new parenteral cephem antibiotic 总被引:1,自引:0,他引:1
M Nakashima T Uematsu M Kanamara K Ueno T Setoyama Y Tomono T Ohno K Okano N Morishita 《Journal of clinical pharmacology》1989,29(2):144-150
The safety and pharmacokinetics of E1040, a new injectable cephem antibiotic, were evaluated in healthy volunteers. In single-dose studies, 125, 250, 500, 1000 and 2000 mg of E1040 were administered by I.V. infusion over 1 hour. Results of 5 minutes I.V. infusions of 500, 1000 and 2000 mg of the drug were also studied. Plasma concentration-time profiles were well suited to a two-compartment open model. The half-life of elimination from plasma was 1.85 +/- 0.16 hours, and the Cmax and AUC paralleled the doses given. The mean urinary recovery within the first 24 hours was 85.7 +/- 6.43% of the dose. In a multiple-dose study, 2000 mg of E1040 (I.V. over 1 hour) was administered every 12 hours (total 9 times) and no abnormal accumulation of the drug in plasma was observed. There were no significant differences in plasma levels or in urinary recoveries between single- and multiple-dose regimens. There were no subjective or objective abnormal findings definitely attributable to the drug except that one subject given 250 mg over 1 hour reported diarrhea, and another complained of nausea during the infusion of 2000 mg over 5 minutes. From these results E1040 was concluded to be safe and well tolerated. 相似文献
13.
14.
We evaluated the safety, tolerance, pharmacokinetics and pharmacodynamics of omeprazole, a new anti-ulcer agent chiefly on the basis of our studies in healthy male volunteers. The type and incidence of side effects of omeprazole have been reported to be similar to those of H2-antagonists, and in our studies too, omeprazole was estimated to be safe and tolerable. Following single doses, the increase in AUC was not proportional to the increase in dosage. In the multiple-dose study, the AUC was greater on day 7 than on day 1. This finding may be due to a partial saturation of first pass elimination. Repeated omeprazole treatment (20 mg once daily for 4 days) inhibited the basal and stimulated acid secretion. Though H2-blockers inhibit the basal and stimulated pepsin secretion, omeprazole inhibited the stimulated pepsin secretion only. 相似文献
15.
Masao Tanaka Hiroyuki Konomi Hiroaki Matsunaga Kazunori Yokohata Naruhiro Utsunomiya Torahiko Takeda 《Journal of Hepato-Biliary-Pancreatic Surgery》1997,4(1):16-19
Technical improvements, such as mechanical lithotripsy, stenting or nasobiliary drainage, and wire-guided cannulation, have reduced the risk of complications in endoscopic sphincterotomy. To determine the extent of this reduction in risk, we assessed the medical records of 1352 patients with common bile duct stones in whom the procedure was conducted. Complications examined were: acute cholangitis and pancreatitis. Stone clearance was achieved in 1256 patients (92.8%), with an overall morbidity rate of 7.7% and a mortality rate of 0.15%. One hundred and forty-two patients had stones with a diameter greater than 20mm; 97 of these patients did not undergo lithotripsy. Cholangitis occurred in 10 of these 97 patients (10.3%), whereas, in the 45 patients who underwent lithotripsy, there were no cases of cholangitis (P=0.02). Stone removal was not immediately accomplished or attempted in 396 patients. In 82 of these patients in whom a stent or a nasobiliary drain was placed in the common bile duct, the incidence of cholangitis was 1.2%, significantly less (P=0.045) than the incidence of 6.4% in the other 314 patients given no stenting or nasobiliary drain. To overcome difficult cannulation, precut sphincterotomy was conducted in 134 patients and wireguided sphincterotomy, a recently introduced procedure, was conducted in 55 patients. When the precutting technique was used, the incidence of acute pancreatitis was significantly higher (8/134; 6.0%) than that in the patients in whom the standard procedure was conducted, i.e., neither the precut technique nor wire-guided ES was used (23/1218; 1.9%) (P=0.008). There were no cases of pancreatitis in the 55 patients in whom wire-guided sphincterotomy was performed, although the difference was not statistically significant because of the small number of patients (P=0.06). Based on these findings, we conclude that improved technologies have led to a significant reduction of complications in endoscopic sphincterotomy. 相似文献
16.
The effects of platelet-derived growth factor (PDGF) on phospholipase D (PLD) activity and deoxyribonucleic acid (DNA) synthesis in rat C6 glioma cells have been investigated. Pretreatment of serum-starved C6 cells with PDGF results in enhanced choline production and the phosphatidylethanol (PEt) formation in the presence of ethanol, indicating the activation of PLD acting on phosphatidylcholine (PC). The dose-response curve for choline generation and DNA synthesis were comparable. In addition, the effects of PDGF on both PEt formation and [3H]thymidine incorporation into acid-precipitable material was blocked by the potent protein kinase C (PKC) inhibitor 1-(5-isoquinolinesulphonyl)-2-methylpiperazine (H-7) but not by N-(2-guanidinoethyl)-5-isoquinolinesulphonamide (HA1004), a relatively weak inhibitor of PKC, suggesting that PDGF plays an important role as a positive regulator of glioma cell growth via a PLD-mediated mitogenic signal transduction cascades, which depends largely on the activation of PKC. 相似文献
17.
Nine healthy subjects received 0.2 mg of beta-methyldigoxin (beta-MD) orally in the fasting state, 30 minutes after and before a standard breakfast. The time-to-peak serum glycoside concentration was delayed and the peak concentration was lower in the postprandial state compared with the other regimens (P less than .01). The absorption rate constant was significantly reduced when beta-MD was given after a meal (1.55 +/- 1.75 hr-1) than before a meal (5.54 +/- 2.16 hr-1) and in the fasting state (5.22 +/- 3.06 hr-1)(P less than .01). Although the area under the serum glycoside concentration-time curve and the cumulative urinary excretion (CUE) of beta-MD, digoxin, and total drug (beta-MD plus digoxin) was not significantly different between three regimens, the CUE infinity tended to be smaller in the postprandial state compared with before a meal. The results indicate that the timing of drug administration in relation to a meal is an important factor leading to the fluctuations of serum glycoside concentration after oral beta-MD, which might be of some clinical importance. 相似文献
18.
We have already developed an arterial thrombosis model in the rat femoral artery which utilized photochemical reaction between systemically injected rose bengal and transillumination of a green light with 540 nm wave length from the outside of the vessel. In the present study, we applied this model to guinea-pigs in order to produce a more suitable thrombus model for evaluation of antithrombotic drugs which act on the prostaglandin cascade. In the guinea-pigs, the irradiated femoral artery was completely occluded in 7 min after the injection of rose bengal (10 mg/kg) in a similar manner to the rats. The processes of primary endothelial injury and the subsequent formation of thrombus during this manipulation were observed by the electron microscopy. Pretreatment with aspirin and Y-20811, a thromboxane synthetase inhibitor, significantly prolonged the time required for occlusion in the guinea-pigs, while these drugs were ineffective in the rats. The antithrombotic effect of vapiprost, a thromboxane A2 receptor antagonist, was more pronounced in the guinea-pigs than the rats. In conclusion, this model in guinea-pigs is more suitable for evaluating antithrombotic drugs, particularly, the action of which is exerted involving the prostaglandin cascade. 相似文献
19.
METHODS. The immunoreactivity of bone GLA protein (BGP) in primary bone tumors, including osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma of bone (MFH), and giant cell tumor of bone (GCT), was investigated with anti-BGP rabbit serum and peroxidase-antiperoxidase complex. RESULTS. As to intracellular localization, BGP antigenicity was detected in 33 of 35 cases of osteosarcoma and 12 of 25 cases of chondrosarcoma. However, there were no positive findings in all 15 cases of MFH or 20 cases of GCT. In chondrosarcoma, the frequency of positively stained cases increased according to pathologic grading (i.e., 3 of 14 cases of Grade 1, 7 of 9 cases of Grade 2, and 2 of 2 cases of Grade 3). Although the multinucleated cells in MFH or GCT were not immunostained, BGP antigenicity was observed in the multinucleated cells of osteosarcoma (12 of 15 cases). In the matrix of osteosarcoma, BGP immunoreactivity of the tumorous osteoid was observed in 28 of 32 cases. However, in the matrices of chondrosarcoma, MFH, and GCT, BGP immunoreactivity was not observed. CONCLUSION. These results suggest that the immunohistochemical study of BGP is useful for the differential diagnosis of bone tumors. 相似文献
20.
J Nagata M Yamauchi K Terabe T Watanabe H Ichihara H Takagi N Nakashima 《Nihon Geka Gakkai zasshi》1987,88(4):489-492
Surgical experience of a rare case of malignant retroperitoneal cyst is reported. A 41-year-old female was admitted on Feb. 26, 1986, complaining of left lower abdominal tumor and mild abdominal pain. She underwent complete removal of an abdominal tumor located at the left flank lateral to the sigmoid colon on March 5. The tumor was well encapsulated, cystic and oval, 12 X 10 X 9 cm in size. Histologic feature of the tumor is classified as mucinous cystadenoma of low grade malignancy by WHO classification. 相似文献