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991.
Pharmacokinetic and pharmacodynamic comparison of fluoropyrimidine derivatives, capecitabine and 5′-deoxy-5-fluorouridine (5′-DFUR) 总被引:3,自引:0,他引:3
Ebi H Sigeoka Y Saeki T Kawada K Igarashi T Usubuchi N Ueda R Sasaki Y Minami H 《Cancer chemotherapy and pharmacology》2005,56(2):205-211
Purpose Capecitabine is a three-step prodrug that was rationally designed to be a more effective and safer alternative to its intermediate metabolite, 5-deoxy-5-fluorouridine (5-DFUR). We compared the pharmacokinetics/pharmacodynamics of these drugs in metastatic breast cancer patients.Methods Six patients received oral capecitabine at 1657 mg/m2 twice daily and 17 received 5-DFUR at 400 mg three times daily. Both drugs were administered for 21 days followed by a 7-day rest.Results Median daily 5-DFUR AUC was significantly higher for capecitabine than for 5-DFUR (81.1 vs 32.6 mmol h/l; P=0.01). Following treatment with 5-DFUR, the median AUC and Cmax of 5-DFUR tended to be higher in patients with a partial response (3.83 g h/ml and 4.88 g/ml) and stable disease (6.46 g h/ml and 4.96 g/ml) than in those with disease progression (2.53 g h/ml and 1.36 g/ml). The AUC and Cmax of 5-DFUR was significantly related to overall survival.Conclusions These results support the superiority of capecitabine over 5-DFUR. 相似文献
992.
Sendo T Sakai N Itoh Y Ikesue H Kobayashi H Hirakawa T Nakano H Oishi R 《Cancer chemotherapy and pharmacology》2005,56(1):91-96
Hypersensitivity reaction (HSR) is still a major concern during cancer chemotherapy with paclitaxel. In the present study, we investigated retrospectively the incidence of HSRs to paclitaxel and the risk factors in 105 patients (553 courses) who received adjuvant chemotherapy (paclitaxel and carboplatin) for ovarian cancer. Moderate to severe HSRs that led to cessation or discontinuation of the chemotherapy, including respiratory distress and hypotension, were observed in 14 patients (13.3%) and 16 courses (2.9%), regardless of the use of conventional premedication with glucocorticoid, and histamine H1 and H2 antagonists. The incidence of HSRs to paclitaxel in patients with ovarian cancer seemed to be considerably higher than those reported by other investigators in patients with other carcinomas such as non-small-cell lung cancer and breast cancer. Four risk factors were identified: (1) history of mild dermal reactions such as facial flushing and urticaria in previous courses, (2) presence of respiratory dysfunction, (3) obesity (body mass index >25), and (4) postmenopausal at the time of ovariectomy. The incidence of hypersensitivity increased linearly as the number of risk factors increased (r=0.992, P=0.008). It is likely that disappearance of the estrous cycle facilitates the occurrence of HSRs to paclitaxel. 相似文献
993.
Ohashi T Takeda A Shigematsu N Kunieda E Ishizaka A Fukada J Deloar HM Kawaguchi O Takeda T Takemasa K Isobe K Kubo A 《International journal of radiation oncology, biology, physics》2005,62(4):1003-1008
PURPOSE: To evaluate long-term pulmonary toxicity of stereotactic radiotherapy (SRT) by pulmonary function tests (PFTs) performed before and after SRT for small peripheral lung tumors. METHODS AND MATERIALS: A total of 17 lesions in 15 patients with small peripheral lung tumors, who underwent SRT between February 2000 and April 2003, were included in this study. Twelve patients had primary lung cancer, and 3 patients had metastatic lung cancer. Primary lung cancer was T1-2N0M0 in all cases. Smoking history was assessed by the Brinkman index (number of cigarettes smoked per day multiplied by number of years of smoking). Prescribed radiation doses at the 80% isodose line were 40-60 Gy in 5-8 fractions. PFTs were performed immediately before SRT and 1 year after SRT. Test parameters included total lung capacity (TLC), vital capacity (VC), forced expiratory volume in 1 s (FEV1.0), and diffusing capacity of lung for carbon monoxide (DLCO). PFT changes were evaluated in relation to patient- and treatment-related factors, including age, the Brinkman index, internal target volume, the percentages of lung volume irradiated with >15, 20, 25, and 30 Gy (V15, V20, V25, and V30, respectively), and mean lung dose. RESULTS: There were no significant changes in TLC, VC, or FEV1.0 before vs. after SRT. The mean percent change from baseline in DLCO was significantly increased by 128.2%. Univariate and multivariate analyses revealed a correlation between DLCO and the Brinkman index. CONCLUSIONS: One year after SRT as compared with before SRT, there were no declines in TLC, VC, and FEV1.0. DLCO improved in patients who had been heavy smokers before SRT, suggesting a correlation between DLCO and smoking cessation. SRT seems to be tolerable in view of long-term lung function. 相似文献
994.
Inhibition of the metabolism of brotizolam by erythromycin in humans: in vivo evidence for the involvement of CYP3A4 in brotizolam metabolism 下载免费PDF全文
Tokairin T Fukasawa T Yasui-Furukori N Aoshima T Suzuki A Inoue Y Tateishi T Otani K 《British journal of clinical pharmacology》2005,60(2):172-175
AIMS: To obtain in vivo evidence for the involvement of cytochrome P450 (CYP) 3A4 in the metabolism of brotizolam. METHODS: Fourteen healthy male volunteers received erythromycin 1200 mg day(-1) or placebo for 7 days in a double-blind randomized crossover manner. On the 6th day they received a single oral 0.5-mg dose of brotizolam, and blood samplings were performed for 24 h. RESULTS: Erythromycin treatment significantly increased the peak plasma concentration (P < 0.05), total area under the plasma concentration-time curve (P < 0.01), and elimination half-life (P < 0.01) of brotizolam. CONCLUSIONS: The present study provides in vivo evidence for the involvement of CYP3A4 in brotizolam metabolism. 相似文献
995.
Aoshima H Miyagisnima A Nozawa Y Sadzuka Y Sonobe T 《International journal of pharmaceutics》2005,293(1-2):25-34
Lubrication properties were compared among glycerin fatty acid esters (Poem TR-FB and Poem TR-HB), magnesium stearate (Mg-St), and a sucrose fatty acid ester (RYOTO SUGAR ESTER S-370F: SSE). Granules containing 50% acetaminophen were prepared, and improvements in their fluidity by the lubricants were compared. The lubricant effects of TR-FB and HB during tablet punching (pressure transmission ratio, ejection force) were similar to those of Mg-St and were better than those of SSE. When the lubricant content, mixing time, and tabletting pressure were changed, TR-FB and TR-HB provided better tablet hardness than Mg-St. TR-FB and TR-HB made tablets more disintegratable than Mg-St. When the effects of these lubricants on the stability of acetylsalicylic acid (ASA) were compared, Mg-St promoted its hydrolysis, but TR-FB or TR-HB did not affect its stability. 相似文献
996.
Igarashi M Takahashi Y Shitara T Nakamura H Naganawa H Miyake T Akamatsu Y 《The Journal of antibiotics》2005,58(5):327-337
Novel antibiotics, active against acid-fast bacteria, caprazamycins, were isolated from the culture broth of Streptomyces sp. MK730-62F2. The planar structures of the compounds were determined by 2D NMR spectroscopic study. Furthermore, the absolute structure of caprazamycin B (2) was established by NMR spectroscopy and X-ray crystallography of its degradation products and by total synthesis of the 5-amino-5-deoxy-D-ribose moiety. In the course of degradation studies of 2 under alkaline and acidic conditions, we obtained the two core components, caprazene (11) and caprazol (14), respectively, in high yield. Structurally, caprazamycins belong to a family of lipouridyl antibiotics, which have been discovered as specific inhibitors of a bacterial translocase. 相似文献
997.
Asaoka Y Sakai H Takahashi N Hirata A Tsukamoto T Yamamoto M Yanai T Masegi T Tatematsu M 《Journal of applied toxicology : JAT》2005,25(6):554-561
In an in vivo 5-week initiation assay model, chemical hepatectomy by hepato-toxicant administration was utilized as a cell proliferation stimulus as an alternative to the two-thirds partial hepatectomy. The study investigated the effect of an intraperitoneal (i.p.) injection of D-galactosamine (D-gal) for this purpose in a medium-term liver bioassay, with a further focus on cell proliferation kinetics and cytochrome P450 (CYP) expression. In experiment I, cell proliferation in rat liver after a single administration of D-gal (700 mg kg(-1), i.p.) was analysed by the bromodeoxyuridine (BrdU) labeling method, and CYP isozymes were quantified by immunoblotting. In experiment II, the induction of glutathione S-transferase placental form (GST-P) positive foci by 1,2-dimethylhydrazine (DMH) was evaluated in a modified in vivo 5-week initiation assay model. At 84 hours after single administration of d-gal (i.p.) the BrdU index was markedly elevated (27.5% +/- 9.5%). Although CYP 2E1 and 1A2 apoprotein contents decreased transiently to less than 20% of the control level, subsequently they recovered to 60% and 40% of the control level, respectively, at 84 hours. Induction of GST-P positive foci in the group given DMH at 84 hours after a single administration of d-gal was significantly greater than in the control group, correlating with the kinetics of cell proliferation. In conclusion, the sensitivity of the present initiation assay using D-gal i.p. is high, so that D-gal i.p. can be considered an effective cell proliferation stimulus. 相似文献
998.
Response to interferon-alpha in chronic hepatitis B with and without precore mutant strain detected by mutation site-specific assay 总被引:4,自引:0,他引:4
Seo Y Yoon S Hamano K Nakaji M Yano Y Katayama M Ninomiya T Hayashi Y Kasuga M 《Journal of clinical gastroenterology》2004,38(5):460-464
GOALS: We investigated whether the presence of precore mutant (stop codon mutation at codon 28) affects the response to interferon-alpha in patients with chronic hepatitis B. BACKGROUND: Mutations of hepatitis B virus (HBV) may influence the response to treatment. The association of precore mutant with the response to interferon is controversial. STUDY: Thirty-one Japanese patients with hepatitis B e antigen-positive chronic hepatitis were treated with natural interferon-alpha. HBV DNA with the precore mutation was assayed in serum using a mutation site-specific assay before and after treatment. RESULTS: Before treatment, precore mutant was detected in 22 cases (group A) and not detected in 9 cases (group B). Serum HBV DNA level before treatment was not different between the 2 groups. At the end of treatment, serum HBV DNA was decreased to undetectable levels in 13% (4 of 31). Six months after treatment, the percentage of cases with loss of hepatitis B e antigen and a decrease in the transaminase level to within the normal range was significantly higher in group B than in group A (67%, 18%, P = 0.015). CONCLUSIONS: Chronic hepatitis without precore mutant strain before treatment is more responsive to IFN-alpha. 相似文献
999.
Sakata Y Yamamoto K Mano T Nishikawa N Yoshida J Hori M Miwa T Masuyama T 《Circulation》2004,109(17):2143-2149
1000.