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Myung Gyoon Lee - One of the best experts on this subject based on the ideXlab platform.

  • effects of acute renal failure induced by uranyl nitrate on the pharmacokinetics of liquiritigenin and its two glucuronides m1 and m2 in rats
    Journal of Pharmacy and Pharmacology, 2010
    Co-Authors: Hee Eun Kang, Myung Gyoon Lee, S I Sohn, S R Baek, Jee W Lee
    Abstract:

    Objectives  Liver disease and acute renal failure (ARF) are closely associated. The pharmacokinetics of liquiritigenin (LQ), a candidate therapy for inflammatory liver disease, and its metabolites M1 and M2 were evaluated in rats with ARF induced by uranyl nitrate (U-ARF rats). Methods  LQ was administered intravenously (20 mg/kg) or orally (50 mg/kg) in U-ARF and control rats, and uridine diphosphate-glucuronosyltransferases (UGT) activity and uridine 5′-diphosphoglucuronic acid (UDPGA) concentrations were determined in the liver and intestine. Key findings  After intravenous LQ administration, U-ARF rats displayed significantly slower LQ renal Clearance but no significant changes in the LQ area under the plasma concentration–time curve (AUC) compared with controls. This was because of similar hepatic UGT activity and UDPGA levels between two groups, which resulted in comparable Non-Renal Clearance, as well as the limited contribution of LQ renal Clearance to total LQ Clearance. However, the AUC and AUCM/AUCLQ ratios of M1 and M2 were significantly increased in U-ARF rats because of decreased urinary excretion of M1 and M2. Similar results were observed following oral administration because of the comparable LQ intestinal metabolism in both groups and decreased urinary excretion of M1 and M2 in U-ARF rats. Conclusions  U-ARF rats displayed decreased urinary excretion of LQ glucuronides, resulting in significantly greater AUC and metabolite ratios of M1 and M2 following LQ administration.

  • slower Clearance of intravenous metformin in rats with acute renal failure induced by uranyl nitrate contribution of slower renal and non renal Clearances
    European Journal of Pharmaceutical Sciences, 2010
    Co-Authors: Young Hee Choi, Inchul Lee, Myung Gyoon Lee
    Abstract:

    It has been reported that metformin was primarily metabolized via hepatic CYP2C11, 2D1, and 3A1/2 in rats. It has also been reported that the protein expression and/or mRNA levels of hepatic CYP2C11, 2D subfamily, and 3A1 have decreased, decreased, and increased, respectively, in U-ARF rats. Thus, pharmacokinetic changes of intravenous metformin in U-ARF rats were evaluated. Metformin was administered intravenously at a dose of 50mg/kg to control and U-ARF rats. After i.v. administration of metformin to U-ARF rats, its time-averaged total body Clearance was significantly slower (95.2% decrease) than controls. This could have been due to both significantly slower time-averaged renal Clearance (99.1% decrease; due to a urine flow rate-dependent timed-interval renal Clearance of the drug, a decrease in renal OCT2, and/or an impaired kidney function in U-ARF rats) and time-averaged Non-Renal Clearance (83.8% decrease; due to a decrease in hepatic CYP2C11 and 2D subfamily in U-ARF rats).

  • faster Clearance of mirodenafil in rats with acute renal failure induced by uranyl nitrate contribution of increased protein expression of hepatic cyp3a1 and intestinal cyp1a1 and 3a1 2
    Journal of Pharmacy and Pharmacology, 2009
    Co-Authors: Young Hee Choi, Young Sun Lee, Tae Kyoung Kim, Bongy Lee, Myung Gyoon Lee
    Abstract:

    Objectives It has been reported that mirodenafil is primarily metabolized via hepatic cytochrome P450 (CYP) 1A1/2, 2B1/2, 2D1 and 3A1/2 in rats. It has also been reported that the protein expression of hepatic CYP3A1 and intestinal CYP1A1 and 3A1/2 increases and that of hepatic CYP2D1 decreases in rats with acute renal failure induced by uranyl nitrate (U-ARF rats). Thus, the pharmacokinetics of mirodenafil were studied in control and U-ARF rats. Methods The pharmacokinetic parameters of mirodenafil and SK3541 (a metabolite of mirodenafil) were compared after the intravenous and oral administration of mirodenafil at a dose of 20 mg/kg to U-ARF and control rats. Key findings After interavenous administration of mirodenafil to U-ARF rats, the total area under the concentration–time curve (AUC) of mirodenafil was significantly smaller (36.5% decrease) than controls, possibly due to the significantly faster Non-Renal Clearance (66.1% increase; because of increase in the protein expression of hepatic CYP3A1) than controls. After the oral administration of mirodenafil to U-ARF rats, the AUC of mirodenafil was also significantly smaller (47.8% decrease) due to the increase in the protein expression of hepatic CYP3A1 and intestinal CYP1A1 and 3A1/2 compared with controls. Conclusions After both intravenous and oral administration of mirodenafil to U-ARF rats, the AUCSK3541/AUCmirodenafil ratios were comparable with that in controls and this could be due to further metabolism of SK3541 in rats.

  • effects of cytochrome p450 inducers and inhibitors on the pharmacokinetics of intravenous furosemide in rats involvement of cyp2c11 2e1 3a1 and 3a2 in furosemide metabolism
    Journal of Pharmacy and Pharmacology, 2009
    Co-Authors: Kyung Yang, Young Hee Choi, Unji Lee, Joo Ho Lee, Myung Gyoon Lee
    Abstract:

    Objectives It has been reported that the Non-Renal Clearance of furosemide was significantly faster in rats pretreated with phenobarbital but was not altered in rats pretreated with 3-methylcholanthrene. However, no studies on other cytochrome P450 (CYP) isozymes have yet been reported in rats. Method Furosemide 20 mg/kg was administered intravenously to rats pretreated with various CYP inducers –3-methylcholanthrene, orphenadrine citrate and isoniazid, inducers of CYP1A1/2, 2B1/2 and 2E1, respectively, in rats – and inhibitors – SKF-525A (a nonspecific inhibitor of CYP isozymes), sulfaphenazole, cimetidine, quinine hydrochloride and troleandomycin, inhibitors of CYP2C6, 2C11, 2D and 3A1/2, respectively, in rats. Key findings The Non-Renal Clearance of furosemide was significantly faster (55.9% increase) in rats pretreated with isoniazid, but slower in those pretreated with cimetidine or troleandomycin (38.5% and 22.7% decreases, respectively), than controls. After incubation of furosemide with baculovirus-infected insect cells expressing CYP2C11, 2E1, 3A1 or 3A2, furosemide was metabolized via CYP2C11, 2E1, 3A1 and 3A2. Conclusions These findings could help explain possible pharmacokinetic changes of furosemide in various rat disease models (where CYP2C11, 2E1, 3A1 and/or CYP3A2 are altered) and drug–drug interactions between furosemide and other drugs (mainly metabolized via CYP2C11, 2E1, 3A1 and/or 3A2).

  • faster Clearance of omeprazole in rats with acute renal failure induced by uranyl nitrate contribution of increased expression of hepatic cytochrome p450 cyp 3a1 and intestinal cyp1a and 3a subfamilies
    Journal of Pharmacy and Pharmacology, 2008
    Co-Authors: Dae Y Lee, Inchul Lee, Young S Jung, Hyun S Shin, Young Choong Kim, Myung Gyoon Lee
    Abstract:

    It has been reported that omeprazole is mainly metabolized via hepatic cytochrome P450 (CYP) 1A1/2, CYP2D1 and CYP3A1/2 in male Sprague-Dawley rats, and the expression of hepatic CYP3A1 is increased in male Sprague-Dawley rats with acute renal failure induced by uranyl nitrate (U-ARF rats). Thus, the metabolism of omeprazole would be expected to increase in U-ARF rats. After intravenous administration of omeprazole (20 mgkg(-1)) to U-ARF rats, the area under the plasma concentration-time curve from time zero to infinity (AUC) was significantly reduced (371 vs 494 microg min mL(-1)), possibly due to the significantly faster Non-Renal Clearance (56.6 vs 41.2 mL min(-1) kg(-1)) compared with control rats. This could have been due to increased expression of hepatic CYP3A1 in U-ARF rats. After oral administration of omeprazole (40 mgkg(-1)) to U-ARF rats, the AUC was also significantly reduced (89.3 vs 235 microg min mL(-1)) compared with control rats. The AUC difference after oral administration (62.0% decrease) was greater than that after intravenous administration (24.9% decrease). This may have been primarily due to increased intestinal metabolism of omeprazole caused by increased expression of intestinal CYP1A and 3A subfamilies in U-ARF rats, in addition to increased hepatic metabolism.

Young Hee Choi - One of the best experts on this subject based on the ideXlab platform.

  • slower Clearance of intravenous metformin in rats with acute renal failure induced by uranyl nitrate contribution of slower renal and non renal Clearances
    European Journal of Pharmaceutical Sciences, 2010
    Co-Authors: Young Hee Choi, Inchul Lee, Myung Gyoon Lee
    Abstract:

    It has been reported that metformin was primarily metabolized via hepatic CYP2C11, 2D1, and 3A1/2 in rats. It has also been reported that the protein expression and/or mRNA levels of hepatic CYP2C11, 2D subfamily, and 3A1 have decreased, decreased, and increased, respectively, in U-ARF rats. Thus, pharmacokinetic changes of intravenous metformin in U-ARF rats were evaluated. Metformin was administered intravenously at a dose of 50mg/kg to control and U-ARF rats. After i.v. administration of metformin to U-ARF rats, its time-averaged total body Clearance was significantly slower (95.2% decrease) than controls. This could have been due to both significantly slower time-averaged renal Clearance (99.1% decrease; due to a urine flow rate-dependent timed-interval renal Clearance of the drug, a decrease in renal OCT2, and/or an impaired kidney function in U-ARF rats) and time-averaged Non-Renal Clearance (83.8% decrease; due to a decrease in hepatic CYP2C11 and 2D subfamily in U-ARF rats).

  • faster Clearance of mirodenafil in rats with acute renal failure induced by uranyl nitrate contribution of increased protein expression of hepatic cyp3a1 and intestinal cyp1a1 and 3a1 2
    Journal of Pharmacy and Pharmacology, 2009
    Co-Authors: Young Hee Choi, Young Sun Lee, Tae Kyoung Kim, Bongy Lee, Myung Gyoon Lee
    Abstract:

    Objectives It has been reported that mirodenafil is primarily metabolized via hepatic cytochrome P450 (CYP) 1A1/2, 2B1/2, 2D1 and 3A1/2 in rats. It has also been reported that the protein expression of hepatic CYP3A1 and intestinal CYP1A1 and 3A1/2 increases and that of hepatic CYP2D1 decreases in rats with acute renal failure induced by uranyl nitrate (U-ARF rats). Thus, the pharmacokinetics of mirodenafil were studied in control and U-ARF rats. Methods The pharmacokinetic parameters of mirodenafil and SK3541 (a metabolite of mirodenafil) were compared after the intravenous and oral administration of mirodenafil at a dose of 20 mg/kg to U-ARF and control rats. Key findings After interavenous administration of mirodenafil to U-ARF rats, the total area under the concentration–time curve (AUC) of mirodenafil was significantly smaller (36.5% decrease) than controls, possibly due to the significantly faster Non-Renal Clearance (66.1% increase; because of increase in the protein expression of hepatic CYP3A1) than controls. After the oral administration of mirodenafil to U-ARF rats, the AUC of mirodenafil was also significantly smaller (47.8% decrease) due to the increase in the protein expression of hepatic CYP3A1 and intestinal CYP1A1 and 3A1/2 compared with controls. Conclusions After both intravenous and oral administration of mirodenafil to U-ARF rats, the AUCSK3541/AUCmirodenafil ratios were comparable with that in controls and this could be due to further metabolism of SK3541 in rats.

  • effects of cytochrome p450 inducers and inhibitors on the pharmacokinetics of intravenous furosemide in rats involvement of cyp2c11 2e1 3a1 and 3a2 in furosemide metabolism
    Journal of Pharmacy and Pharmacology, 2009
    Co-Authors: Kyung Yang, Young Hee Choi, Unji Lee, Joo Ho Lee, Myung Gyoon Lee
    Abstract:

    Objectives It has been reported that the Non-Renal Clearance of furosemide was significantly faster in rats pretreated with phenobarbital but was not altered in rats pretreated with 3-methylcholanthrene. However, no studies on other cytochrome P450 (CYP) isozymes have yet been reported in rats. Method Furosemide 20 mg/kg was administered intravenously to rats pretreated with various CYP inducers –3-methylcholanthrene, orphenadrine citrate and isoniazid, inducers of CYP1A1/2, 2B1/2 and 2E1, respectively, in rats – and inhibitors – SKF-525A (a nonspecific inhibitor of CYP isozymes), sulfaphenazole, cimetidine, quinine hydrochloride and troleandomycin, inhibitors of CYP2C6, 2C11, 2D and 3A1/2, respectively, in rats. Key findings The Non-Renal Clearance of furosemide was significantly faster (55.9% increase) in rats pretreated with isoniazid, but slower in those pretreated with cimetidine or troleandomycin (38.5% and 22.7% decreases, respectively), than controls. After incubation of furosemide with baculovirus-infected insect cells expressing CYP2C11, 2E1, 3A1 or 3A2, furosemide was metabolized via CYP2C11, 2E1, 3A1 and 3A2. Conclusions These findings could help explain possible pharmacokinetic changes of furosemide in various rat disease models (where CYP2C11, 2E1, 3A1 and/or CYP3A2 are altered) and drug–drug interactions between furosemide and other drugs (mainly metabolized via CYP2C11, 2E1, 3A1 and/or 3A2).

Inchul Lee - One of the best experts on this subject based on the ideXlab platform.

  • effects of poloxamer 407 induced hyperlipidemia on the pharmacokinetics of carbamazepine and its 10 11 epoxide metabolite in rats impact of decreased expression of both cyp3a1 2 and microsomal epoxide hydrolase
    European Neuropsychopharmacology, 2012
    Co-Authors: Young Sun Lee, Inchul Lee, Young Woo Kim, Sang Geon Kim, Myung Gull Lee, Hee Eun Kang
    Abstract:

    The pharmacokinetics of carbamazepine (CBZ) and its active 10,11-epoxide metabolite (CBZ-E) were evaluated after intravenous and oral administration of 5 mg/kg CBZ to rats with hyperlipidemia induced by poloxamer 407 (HL rats) and controls. The total area under the plasma concentration-time curve (AUC) of CBZ in HL rats after intravenous administration was significantly greater than that in controls due to their slower Non-Renal Clearance (CL(NR)). This was due to slower hepatic CL(int) for metabolism of CBZ to CBZ-E in HL rats via CYP3A1/2. This result was consistent with a previous study indicating reduced hepatic CYP3A1/2 expression in HL rats. Interestingly, the AUC of CBZ-E was also increased in HL rats, while AUC(CBZ-E)/AUC(CBZ) ratios remained unchanged. These results suggested that further metabolism of CBZ-E to the inactive metabolite trans-10,11-dihydoxyl-10,11-dihydro-CBZ (CBZ-D) via microsomal epoxide hydrolase (mEH) was also slowed in HL rats. The significantly reduced hepatic mRNA level and expression of mEH protein in HL rats compared to controls confirmed the above hypothesis. Similar pharmacokinetic changes were observed in HL rats after oral administration of CBZ. These findings have potential therapeutic implications assuming that the HL rat model qualitatively reflects similar changes in patients with hyperlipidemia. Caution is required regarding pharmacotherapy in the hyperlipidemic state in cases where drugs that are metabolized principally by CYP3A1/2 or mEH and have a narrow therapeutic range are in use.

  • pharmacokinetics of liquiritigenin and its two glucuronides m1 and m2 in rats with acute hepatitis induced by d galactosamine lipopolysaccharide or ccl 4
    Xenobiotica, 2010
    Co-Authors: Hee Eun Kang, Yeonhee Kim, S I Sohn, S R Baek, Jeosoon Lee, Seongyong Kim, Inchul Lee, Moongyu Lee
    Abstract:

    Cytoprotective effects of liquiritigenin (LQ) against liver injuries have been reported, but its pharmacokinetics has not been studied in acute hepatitis. Thus, pharmacokinetics of LQ and its two conjugated glucuronide metabolites: 4'-O-glucuronide (M1) and 7-O-glucuronide (M2), in rats with acute hepatitis induced by d-galactosamine/lipopolysaccharide (GalN/LPS) rats or carbon tetrachloride-treated (CCl(4)-treated) rats were evaluated. LQ was administered intravenously (20 mg kg(-1)) and orally (50 mg kg(-1)) to control GalN/LPS and CCl(4)-treated rats. Expression of uridine 5'-diphospho-glucuronosyltransferases 1A (UGT1A) and in vitro metabolism of LQ in hepatic and intestinal microsomes were also measured. After intravenous administration of LQ, area under the plasma concentration-time curve (AUC) of LQ in GalN/LPS rats was significantly smaller than that in controls due to faster Non-Renal Clearance, as a result of its greater free fraction in plasma and faster hepatic blood flow rate than the controls. In CCl(4)-treated rats, the AUC(M1, 0-8 h)/AUC(LQ) and AUC(M2, 0-8 h)/AUC(LQ) ratios were significantly greater than the controls due to decrease in biliary excretion of M1 and M2. However, no significant pharmacokinetic changes were observed in both acute hepatitis rats after oral administration due to comparable intestinal metabolism of LQ. Modification of oral dosage regimen of LQ may not be necessary in patients with acute hepatitis; but human studies are required.

  • slower Clearance of intravenous metformin in rats with acute renal failure induced by uranyl nitrate contribution of slower renal and non renal Clearances
    European Journal of Pharmaceutical Sciences, 2010
    Co-Authors: Young Hee Choi, Inchul Lee, Myung Gyoon Lee
    Abstract:

    It has been reported that metformin was primarily metabolized via hepatic CYP2C11, 2D1, and 3A1/2 in rats. It has also been reported that the protein expression and/or mRNA levels of hepatic CYP2C11, 2D subfamily, and 3A1 have decreased, decreased, and increased, respectively, in U-ARF rats. Thus, pharmacokinetic changes of intravenous metformin in U-ARF rats were evaluated. Metformin was administered intravenously at a dose of 50mg/kg to control and U-ARF rats. After i.v. administration of metformin to U-ARF rats, its time-averaged total body Clearance was significantly slower (95.2% decrease) than controls. This could have been due to both significantly slower time-averaged renal Clearance (99.1% decrease; due to a urine flow rate-dependent timed-interval renal Clearance of the drug, a decrease in renal OCT2, and/or an impaired kidney function in U-ARF rats) and time-averaged Non-Renal Clearance (83.8% decrease; due to a decrease in hepatic CYP2C11 and 2D subfamily in U-ARF rats).

  • faster Clearance of omeprazole in rats with acute renal failure induced by uranyl nitrate contribution of increased expression of hepatic cytochrome p450 cyp 3a1 and intestinal cyp1a and 3a subfamilies
    Journal of Pharmacy and Pharmacology, 2008
    Co-Authors: Dae Y Lee, Inchul Lee, Young S Jung, Hyun S Shin, Young Choong Kim, Myung Gyoon Lee
    Abstract:

    It has been reported that omeprazole is mainly metabolized via hepatic cytochrome P450 (CYP) 1A1/2, CYP2D1 and CYP3A1/2 in male Sprague-Dawley rats, and the expression of hepatic CYP3A1 is increased in male Sprague-Dawley rats with acute renal failure induced by uranyl nitrate (U-ARF rats). Thus, the metabolism of omeprazole would be expected to increase in U-ARF rats. After intravenous administration of omeprazole (20 mgkg(-1)) to U-ARF rats, the area under the plasma concentration-time curve from time zero to infinity (AUC) was significantly reduced (371 vs 494 microg min mL(-1)), possibly due to the significantly faster Non-Renal Clearance (56.6 vs 41.2 mL min(-1) kg(-1)) compared with control rats. This could have been due to increased expression of hepatic CYP3A1 in U-ARF rats. After oral administration of omeprazole (40 mgkg(-1)) to U-ARF rats, the AUC was also significantly reduced (89.3 vs 235 microg min mL(-1)) compared with control rats. The AUC difference after oral administration (62.0% decrease) was greater than that after intravenous administration (24.9% decrease). This may have been primarily due to increased intestinal metabolism of omeprazole caused by increased expression of intestinal CYP1A and 3A subfamilies in U-ARF rats, in addition to increased hepatic metabolism.

Wan G Shin - One of the best experts on this subject based on the ideXlab platform.

  • pharmacokinetics and pharmacodynamics of azosemide after intravenous and oral administration to rats with alloxan induced diabetes mellitus
    Journal of Pharmacy and Pharmacology, 1996
    Co-Authors: Kwang J Park, Woo H Yoon, Wan G Shin
    Abstract:

    Because physiological changes occurring in diabetes mellitus patients could alter the pharmacokinetics and pharmacodynamics of the drugs used to treat the disease, the pharmacokinetics and pharmacodynamics of azosemide were investigated after intravenous and oral administration of the drug (10 mg kg -1 ) to control and alloxan-induced diabetes mellitus rats (AIDRs). After intravenous administration of azosemide to the AIDRs, the area under the plasma concentration-time curve (AUC) increased considerably (3120 compared with 2520 μg min mL -1 ; P < 0.135) and the total body Clearance decreased considerably (3.20 compared with 3.96 mL min -1 kg -1 ; P < 0.0593). The considerable reduction in time-averaged total body Clearance in the AIDRs was a result of the significant decrease in renal Clearance (1.01 compared with 1.55 mL min -1 kg -1 ) in the AIDRs, the Non-Renal Clearance being comparable between the two groups of rats. After intravenous administration, the 8-h urinary excretion of azosemide (29.5 compared with 40% of intravenous dose ; P < 0.0883) and one of its metabolites, M1 (2.15 compared with 2.60% of intravenous dose, expressed in terms of azosemide ; P < 0.05) decreased in the AIDRs because of the impaired kidney function. The diuretic, natriuretic, kaliuretic and chloruretic efficiencies increased significantly in the AIDRs. After oral administration of azosemide, AUC decreased significantly in the AIDRs (115 compared with 215 μg min mL -1 ) possibly because of the reduced gastrointestinal absorption of azosemide in the AIDRs. After oral administration of azosemide, the 8-h urine output decreased significantly in the AIDRs (9.32 compared with 16.1 mL per 100 g body weight) because of the significantly reduced 8-h urinary excretion of azosemide (3.00 compared with 9.14% of oral dose). After both intravenous and oral administration some pharmacokinetic and pharmacodynamic parameters of azosemide were significantly different in AIDRs.

Kwang J Park - One of the best experts on this subject based on the ideXlab platform.

  • pharmacokinetics and pharmacodynamics of azosemide after intravenous and oral administration to rats with alloxan induced diabetes mellitus
    Journal of Pharmacy and Pharmacology, 1996
    Co-Authors: Kwang J Park, Woo H Yoon, Wan G Shin
    Abstract:

    Because physiological changes occurring in diabetes mellitus patients could alter the pharmacokinetics and pharmacodynamics of the drugs used to treat the disease, the pharmacokinetics and pharmacodynamics of azosemide were investigated after intravenous and oral administration of the drug (10 mg kg -1 ) to control and alloxan-induced diabetes mellitus rats (AIDRs). After intravenous administration of azosemide to the AIDRs, the area under the plasma concentration-time curve (AUC) increased considerably (3120 compared with 2520 μg min mL -1 ; P < 0.135) and the total body Clearance decreased considerably (3.20 compared with 3.96 mL min -1 kg -1 ; P < 0.0593). The considerable reduction in time-averaged total body Clearance in the AIDRs was a result of the significant decrease in renal Clearance (1.01 compared with 1.55 mL min -1 kg -1 ) in the AIDRs, the Non-Renal Clearance being comparable between the two groups of rats. After intravenous administration, the 8-h urinary excretion of azosemide (29.5 compared with 40% of intravenous dose ; P < 0.0883) and one of its metabolites, M1 (2.15 compared with 2.60% of intravenous dose, expressed in terms of azosemide ; P < 0.05) decreased in the AIDRs because of the impaired kidney function. The diuretic, natriuretic, kaliuretic and chloruretic efficiencies increased significantly in the AIDRs. After oral administration of azosemide, AUC decreased significantly in the AIDRs (115 compared with 215 μg min mL -1 ) possibly because of the reduced gastrointestinal absorption of azosemide in the AIDRs. After oral administration of azosemide, the 8-h urine output decreased significantly in the AIDRs (9.32 compared with 16.1 mL per 100 g body weight) because of the significantly reduced 8-h urinary excretion of azosemide (3.00 compared with 9.14% of oral dose). After both intravenous and oral administration some pharmacokinetic and pharmacodynamic parameters of azosemide were significantly different in AIDRs.