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Lee, Chang Hyun,Goo, Jin Mo,Bae, Kyongtae T.,Lee, Hyun Ju,Kim, Kwang Gi,Chun, Eun Ju,Park, Chang Min,Im, Jung-Gi J.B. Lippincott 2007 Vol. No.
OBJECTIVE:: To investigate the effect of saline chase injected at 2 different rates on computed tomography (CT) angiography. MATERIALS AND METHODS:: This study was approved by our institutional animal study committee. Three injection protocols were used; contrast injection (24 mL, 0.8 mL/s) without saline chase (protocol A), contrast injection with saline chase injected at the same rate as the contrast medium (protocol B), and contrast injection with saline chase injected at half the rate (0.4 mL/s) of the contrast medium (protocol C). In the 3 dogs used in our study, each of the protocols was applied twice for every dog resulting in a total of 18 sessions of monitoring scans. CT images were acquired every second at the fixed level of the aorta and pulmonary artery (PA). The duration of plateau, plateau deviation, and peak arterial enhancement were computed and compared using the Kruskall–Wallis and Mann–Whitney U test. RESULTS:: Peak contrast enhancements were significantly more delayed with protocol B than with protocol A in both the PA (B: 48 seconds, A: 30 seconds, P = 0.024) and aorta (B: 46 seconds, A: 38 seconds, P = 0.024). The duration of enhancement plateau was longer with protocol B than with protocol A in PA (B: 14.8 seconds, A: 9.0 seconds, P = 0.002) and in aorta (B: 16.2 seconds, A: 11.6 seconds, P = 0.004). Protocol C had the longest duration of plateau in both PA (34.5 seconds, P = 0.002) and aorta (33.8 seconds, P = 0.004) with uniform plateau enhancement. The peak enhancement values of protocol C, however, were substantially lower than that of protocol A and B in both the PA (A: 262 HU, B: 239 HU, C: 191 HU, P = 0.001) and aorta (A: 263 HU, B: 268 HU, C: 210 HU, P = 0.001). CONCLUSIONS:: Saline chase prolongs the duration of plateau and delays peak enhancement of the pulmonary artery and aorta. Saline chase injected at half the rate of contrast medium injection allowed more uniform and prolonged plateau contrast enhancement than other protocols.
Lee, SeungHwan,Kim, Bo-Hyung,Nam, Won-Seok,Yoon, Seo Hyun,Cho, Joo-Youn,Shin, Sang-Goo,Jang, In-Jin,Yu, Kyung-Sang J.B. Lippincott Co. [etc.] 2012 The Journal of clinical pharmacology Vol.52 No.2
<P>The current study assessed the influence of the CYP2C19 genotype on the pharmacokinetics and tolerability of voriconazole after single and multiple oral doses in healthy volunteers. Six subjects for the CYP2C19 homozygous extensive metabolizer (EMs), 6 for heterozygous extensive metabolizer (HEMs), and 6 for poor metabolizer (PMs) were enrolled, and their CYP2C9, CYP3A5, and MDR1 genotypes were analyzed. After a single intravenous infusion or single and multiple oral doses of 200 mg of voriconazole, plasma concentrations of voriconazole were measured. Bioavailability was not significantly different among the CYP2C19 genotypes. Voriconazole exposure in PMs was approximately 3 times higher compared with EMs after a single intravenous or oral dose. At steady state, the plasma concentration just before the next dosing and area under the concentration-time curve from dosing to the time point of the next dosing for PMs were about 5 times and 3 times higher than EMs, respectively. These results suggest that the CYP2C19 genotype is the major determinant of the wide PK variability of voriconazole.</P>
Postgastrectomy pharmacokinetic changes of S-1 in patients with localized advanced gastric cancer.
Lim, Hyeong-Seok,Ryu, Keun Won,Lee, Jun Ho,Kim, Young-Woo,Ju Choi, Il,Kim, Mi-Jung,Park, Young-Iee,Hwang, Aekyung,Park, Sook Ryun J.B. Lippincott Co. [etc.] 2015 The Journal of Clinical Pharmacology Vol.55 No.8
<P>S-1 is an oral 5-fluorouracil agent containing tegafur, 5-chloro-2, 4-dihydroxypyridine (CDHP), and potassium oxonate. This study explored the pharmacokinetics of S-1 and pharmacokinetic changes after gastric surgery in patients with resectable gastric cancer who received pre- and postoperative S-1 plus docetaxel. Serial blood was drawn before and after gastrectomy from 37 patients for pharmacokinetic analysis. The pharmacokinetics of tegafur, 5-fluorouracil, and CDHP were analyzed by noncompartmental analysis (NCA) methods and by modeling. In modeling analysis, CHDP concentrations were incorporated in the model as a time-varying covariate that inhibits the clearance of 5-fluorouracil following an inhibitory Emax model. In NCA, the pharmacokinetics of tegafur and 5-FU before and after gastric surgery were similar, although average maximum concentrations of 5-FU were decreased with statistical significance after gastrectomy. Median Tmax of tegafur was shorter after surgery without statistical significance. In modeling analysis, tegafur was best fitted by mixed zero and first-order absorption. The only difference in the final pharmacokinetic model around gastrectomy was the presence of an absorption lag of 0.23 hours before surgery. Incorporation of CDHP concentrations significantly improved the model. Although some pharmacokinetic results showed statistically significant changes after gastrectomy, these differences seem to be too small to have any clinical implication.</P>
Colloidal Gold Nanoparticles as a Blood-Pool Contrast Agent for X-ray Computed Tomography in Mice
Cai, Quan-Yu,Kim, Sun Hee,Choi, Kyu Sil,Kim, Soo Yeon,Byun, Seung Jae,Kim, Kyoung Woo,Park, Seong Hoon,Juhng, Seon Kwan,Yoon, Kwon-Ha J.B. Lippincott 2007 Vol. No.
OBJECTIVES:: To present the pharmacokinetics and computed tomographic imaging efficacy of colloidal gold nanoparticles (AuNPs) as a blood-pool agent for x-ray computed tomography (CT). METHODS AND MATERIALS:: To prepare the colloidal AuNPs, gold nanocrystals were modified using sulfhydrated polyethylene glycol (PEG). Cytotoxicity and histopathologic tests were carried out for toxicity evaluation. Six adult Balb/c mice underwent microcomputed tomography scans after injection of colloidal AuNPs (2.5 μmol Au/g body weight). Four mice with HT-1080 tumors were imaged for visualization of the tumor vasculature. RESULTS:: The PEG coated colloidal AuNPs appeared as spherical nanoparticles with 38-nm diameters. The AuNPs-PEG showed a biocompatibility without toxicity in the mice. We identified a stable imaging window for visualizing the vasculature system, immediately to 24 hours after injection. Microcomputed tomography imaging using AuNPs-PEG clearly visualized the tumor vascular structures. CONCLUSION:: Colloidal AuNPs show potential as a blood-pool agent for x-ray CT imaging.
Kim, Ho-Sook,Cho, Doo-Yeoun,Park, Bo-Min,Bae, Soo-Kyoung,Yoon, Yune-Jung,Oh, Minkyung,Ghim, Jong-Lyul,Kim, Eun-Young,Kim, Dong-Hyun,Shin, Jae-Gook J.B. Lippincott Co. [etc.] 2014 The Journal of Clinical Pharmacology Vol.54 No.8
<P>We evaluated the effect of CYP2C19 genotype over time on the antiplatelet response of clopidogrel in healthy subjects. Seventy subjects enrolled for a pharmacodynamic study and 22 subjects for a pharmacokinetic and pharmacodynamic study took 300?mg clopidogrel on the first day and 75?mg once daily for six consecutive days. The subjects with CYP2C19 poor metabolizers (PM, N?=?22) and intermediate metabolizers (IM, N?=?37) had significantly delayed time to inhibition of platelet aggregation (IPA) compared with CYP2C19 extensive metabolizers (EM, N?=?33) (12 vs. 9 vs. 2?hours as median Tmax , P?<?.05) after a 300?mg of clopidogrel. During maintenance doses of clopidogrel, IPA values of only CYP2C19 PM subjects were gradually decreased from 30.0??21.9% on day 2 to 23.7??16.6% on day 8 (P?>?.05 for time effect; P?<?.05 for time and genotype interaction effect). CYP2C19 PM had decreased Cmax and AUC of thiol metabolite compared with CYP2C19 EM (0.42- and 0.37-fold on day 1, P?<?.01; 0.39- and 0.34-fold on day 7, P?<?.01, respectively). Delayed time to reach maximal IPA as well as decreased IPA may influence the increased risk of the acute cardiac events in CYP2C19 PM and IM.</P>