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테트라메톡시프라본이 파크리탁셀의 약물동태에 미치는 영향
나종학,백채선,최준식 대한약학회 2004 약학회지 Vol.48 No.4
The pharmacokinetics of orally administered paclitlxel (50 mg/kg) was studied in six rabbits after 1hr pretreatment (2.0 mg/kg and 10 mg/kg) of tetramethoxyflavone or coadministration of (2.0 mg/kg, 10 mg/kg and 20 mg/kg) tetramethoxyflavone. The area under the plasma concentration-tine curve (AUC) and plasma concentration of paclitaxe1 coadministered with tetramethoxyflavone (10 mglkg) were increased significantly (p<0.05) compared with control. However, coadministration of tetramethoxyflavone (2 and 20 mg/kg) showed no significant effect on the pharmacokinetic parameters of paclitaxel. Pretreatment with tetramethoxyflavone significantly (p<0.05) increased the plasma concentration of paclitaxel. The area under the plasma concentration-time curve (AUC) and the peak concentration (C$_{max}$) of paclitaxel pretreated with tetramethoxyflavone were increased significantly (p<0.01, p<0.05) compared with control. The terminal half. life of paclitaxel pretreated with tetramethoxyflavone (2 mg/kg and 10 mg/kg) was significantly (p<0.05) prolonged compared with control. Pretreatment with tetramethoxyflavone (2.0 mg/kg, 10 mg/kg) significantly (p<0.01, p<0.05) increased the absolute bioavailability of paclitaxel compared with the control (154∼179%). On the basis of the results, it might be considered that tetramethoxyflavone may inhibit cytochrome P450 or P-glycoprotein efflux pump which are engaged in paclitaxel metabolism, result in increased AUC and t$_{1}$2/ of paclitaxel. However, further study should be conducted to clarify the roles of cytochrome P450 and P-glycoprotein on paclitaxel bioavailability with/or without tetramethoxyflavone. P-glycoprotein on paclitaxel bioavailability with/or without tetramethoxyflavone.
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나종학,최준식 한국약제학회 2005 Journal of Pharmaceutical Investigation Vol.35 No.2
The pharmacokinetics of oral nifedipine (5 mg/kg) was studied in rabbits given after or simultaneously with naringin (1.5, 7.5 and 15 mg/kg, respectively). The area under the plasma concentration-time curve (AUC) and the peak concentration (C_(max)) of nifedipine coadrninistered or pretreated with naringin were significantly increased (p < 0.05, coad.; p < 0.01, pret.) compared with the control group. The absolute bioavailability (AB%) of nifedipine was significantly (p < 0.05, coad.; p < 0.01, pret.) higher by 22.3 - 28.1% compared to the control (17.9%). The relative bioavailability (RB%) of nifedipine was higher by 1.24 - 1.43 times (coad.) and 1.32 - 1.57 times (pret.) than those of the control, showing that preatreatment of naringin was more effective than that of the coadministration of naringin. Naringin did not show significant effect on the Tmax and t_(1/2) of nifedipine. It is suggested that naringin may alter pharmacokinetic paramiters of nifedipine by inhibition of P-glycoprotein efflux pump and its first-pass metabolism. The dosage of nifedipine should be adjusted when it is administered with naringin in a clinical situation.
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토끼의 신장기능에 미치는 K+ Channel 차단제인 Glibenclamide 의 영향
고석태(Suk Tai Ko),나종학(Jong Hak Na) 한국응용약물학회 2001 Biomolecules & Therapeutics(구 응용약물학회지) Vol.9 No.1
This study was investigated about the effect of glibenclamide (GLY) which is K^+ channel blocker on renal function in rabbit, GLY, when given into the vein, produced the diuretic action accompanied with the increases of amounts of Na^+ and K^+ excreted into urine (E_(Na), E_K), and then osmolar and negative free water clearances (C_(osm), `T^c_(H2O)), fraction excretory rates of filtered Na^+ and K^+ (F_(Na), F_K) and ratios of E_K against E_(Na) were augmented. Filtration fraction (FF) were reduced because renal plasma flow (RPF) were not changed but glomerular filtration rates (GFR) were diminished. GLY administered into a renal artery exhibited significant reduction of urine volume along with the decreases of GFR and RPF in only experimented kidney whereas changes of renal function was not observed in control kidney. GLY given intracerebroventricularly exhibited diuretic action along with the increase of E_(Na), E_K and F_(Na), F_K by small dose which was not affect on renal function when it given into the vein. Above results suggest that GLY given into the vein in rabbit produce the diuretic action by inhibition of electrolytes reabsorption in renal tubules through central function.
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