scholarly journals Effect of CYP3A1(23) Induction on Clarithromycin Pharmacokinetics in Rats with Diabetes Mellitus

2005 ◽  
Vol 49 (6) ◽  
pp. 2528-2532 ◽  
Author(s):  
Yu C. Kim ◽  
Joo H. Lee ◽  
So H. Kim ◽  
Myung G. Lee
Keyword(s):  
Diabetes Mellitus ◽  
Body Weight ◽  
Oral Administration ◽  
Mrna Level ◽  
Area Under The Curve ◽  
Intrinsic Clearance ◽  
Diabetic Rat ◽  
Intravenous And Oral Administration ◽  
Pharmacokinetics In Rats

ABSTRACT After intravenous and oral administration of clarithromycin at a dose of 20 mg/kg of body weight to rats with diabetes mellitus induced by alloxan (DMIA) and diabetes mellitus induced by streptozotocin (DMIS), the area under the curve values were significantly smaller than those of respective control rats. The in vitro intrinsic clearance values for the disappearance of clarithromycin were significantly faster in both rats with DMIA and rats with DMIS than in control rats. The above data suggested that metabolism of clarithromycin increased in both types of diabetic rat due to an increase in the expression and mRNA level of CYP3A1(23) in the rats.

scholarly journals Changes in omeprazole pharmacokinetics in rats with diabetes induced by alloxan or streptozotocin: Faster clearance of omeprazole due to induction of hepatic CYP1A2 and 3A1

2007 ◽  
Vol 10 (4) ◽  
pp. 420 ◽  
Author(s):  
Dae Young Lee ◽  
Myung G. Lee ◽  
Hyun Sook Shin ◽  
Inchul Lee
Keyword(s):  
Diabetes Mellitus ◽  
Oral Administration ◽  
Intravenous Administration ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Mrna Levels ◽  
First Pass ◽  
Metabolic Activities ◽  
Intravenous And Oral Administration ◽  
Pharmacokinetics In Rats

Purpose. To investigate the effect of diabetes mellitus induced by alloxan (DMIA) or streptozotocin (DMIS) on the pharmacokinetics of omeprazole in rats. It has been reported that omeprazole is primarily metabolized via hepatic CYP1A2, 2D1, and 3A1 in rats. The expression and mRNA levels of hepatic CYP1A2 and 3A1 increases in DMIA and DMIS rats, but the expression of hepatic CYP2D1 does not change in DMIS rats. In addition, the metabolic activities of intestinal CYP3A1/2 decreases in DMIS rats. Thus, it could be expected that the pharmacokinetics of omeprazole would be affected by changes in both DMIA and DMIS. Methods. Omeprazole was administered intravenously (20 mg/kg) and orally (40 mg/kg) to DMIA and DMIS rats and their respective controls. Results. After intravenous administration of omeprazole, the CLNR of the drug was significantly faster in DMIA (52.6 versus 67.4 mL/min/kg) and DMIS (50.2 versus 73.0 mL/min/kg) rats than the respective controls. However, after oral administration of omeprazole, the AUC was comparable between each type of diabetic rat and the respective controls. Conclusions. The significantly faster CLNR of intravenous omeprazole could be due to increased expression and mRNA levels of hepatic CYP1A2 and 3A1 in both types of diabetic rat. The comparable AUC of oral omeprazole could be due to a decrease in the intestinal first-pass effect of omeprazole caused by decreased intestinal CYP3A1/2 in diabetic rats. Following both intravenous and oral administration in DMIA and DMIS rats, the pharmacokinetics of omeprazole were similarly altered.

scholarly journals Effects of Diabetes Mellitus Induced by Alloxan on the Pharmacokinetics of Metformin in Rats: Restoration of Pharmacokinetic Parameters to the Control State by Insulin Treatment

2008 ◽  
Vol 11 (1) ◽  
pp. 88 ◽  
Author(s):  
Myung G. Lee ◽  
Young H Choi ◽  
Inchul Lee
Keyword(s):  
Diabetes Mellitus ◽  
Oral Administration ◽  
Protein Expression ◽  
Intravenous Administration ◽  
Insulin Treatment ◽  
Pharmacokinetic Parameters ◽  
Mrna Levels ◽  
Altered Pharmacokinetic ◽  
Intravenous And Oral Administration ◽  
Control State

To test the effect of insulin treatment on the pharmacokinetics of metformin in rats with diabetes mellitus induced by alloxan (DMIA rats). The following results were reported from other studies. Metformin was metabolized via hepatic CYP2C11, 2D1, and 3A1/2 in rats. In DMIA rats, the protein expression and mRNA levels of hepatic CYP2C11 and 3A1/2 decreased and increased, respectively. In rat model of diabetes mellitus induced by streptozotocin, the protein expression of hepatic CYP2D1 was not changed. The increase in hepatic CYP1A2, 2B1, and 2E1, and decrease in hepatic CYP2C11 in DMIA rats was returned to the controls by insulin treatment. METHODS. Metformin (100 mg/kg) was administered intravenously and orally to the control rats, DMIA rats, and DMIA rats with insulin treatment for 3 weeks (DMIA rats with insulin). RESULTS. After intravenous administration of metformin to the DMIA rats, the CLR and CLNR of the drug were significantly slower than the controls. After oral administration of metformin to the DMIA rats, the AUC of the drug was also significantly greater than the controls. After intravenous administration of metformin to the DMIA rats with insulin, the significantly slower CLNR of the drug in the DMIA rats was returned to the controls. The altered pharmacokinetic indices observed following intravenous and oral administration of metformin to DMIA rats returned to the control values in the DMIA rats with insulin. CONCLUSIONS. The significantly slower CLNR of metformin in the DMIA rats could be due to the decrease in hepatic CYP2C11 than the controls. The comparable CLNR of metformin between the DMIA rats with insulin and the control rats could be due to restoration of hepatic CYP enzyme changes in DMIA rats to the controls.

scholarly journals In vivo Neurological, Analgesic and In vitro Antioxidant and Cytotoxic Activities of Ethanolic Extract of Leaf and Stem Bark of Wedelia chinensis

2019 ◽  
Vol 22 (1) ◽  
pp. 18-26
Author(s):  
Sayema Khanum ◽  
Md Shahid Sarwar ◽  
Mohammad Safiqul Islam
Keyword(s):  
Body Weight ◽  
Oral Administration ◽  
Radical Scavenging ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
Pharmaceutical Journal ◽  
Stem Bark ◽  
Cytotoxic Activities

Wedelia chinensis is a widely used anti-inflammatory and hepatoprotective medicinal plant in Bangladesh. In this study, analgesic, neurological, antioxidant and cytotoxic activities of the ethanolic extract of leaf and stem bark of W. chinensis were investigated. Oral administration of the ethanolic extract of W. chinensis (200- and 300-mg/kg body weight) was investigated on animal model for neurological activity using open field test and hole cross test. Acetic acid induced writhing method was used to assess the analgesic activity. DPPH (1,1-diphenyl, 2-picryl hydrazyl) radical scavenging assay was used for determining the antioxidant activity, while brine shrimp lethality bioassay was used for investigating cytotoxicity. The ethanol extract of the plant produced significant reduction (P<0.05) of locomotion in both doses (200- and 300-mg/kg body weight) indicating pronounced neurological activity. Oral administration of alcoholic leaves and stem extracts significantly (p < 0.05) inhibited writhing response in mice. The percentage of scavenging of DPPH free radical was found to be concentration dependent with IC50 value of 44.10 ± 0.65 and 38.96 ± 0.50 μg/ml for leaves and stem extracts, respectively. Our findings indicate that W. chinensis may be a source of natural antioxidant with potent analgesic, neurological and cytotoxic activities. Bangladesh Pharmaceutical Journal 22(1): 18-26, 2019

scholarly journals Experimental study on the effects of Kursi Ziyabet on the rat model of diabetes mellitus

2019 ◽  
Vol 02 (01) ◽  
pp. 7-11
Author(s):  
Alimjan Parhat ◽  
Haibaier Huojiaaihemaiti ◽  
Nabijan Mohammadturusn ◽  
Mammat Nurahmat
Keyword(s):  
Diabetes Mellitus ◽  
Body Weight ◽  
Blood Sugar ◽  
Water Intake ◽  
Fasting Blood Sugar ◽  
Diabetic Rat ◽  
Intragastric Administration ◽  
Model Group ◽  
Rat Models ◽  
Significant Difference

Objective: To evaluate the hyperglycemic effects of Kursi Ziyabet (KZ) tablets on the rat models of diabetes mellitus. Methods: In total, 58 male SD rats were assigned randomly to six groups. All except the normal group were transformed into experimental diabetes mellitus rat models by injecting streptozocin. The hyperglycemic effect and the mechanism of Ziyabet were evaluated by body weight, food and water intake, fasting blood sugar, and related parameters by measuring the oxidative stress-related factors and lipid metabolism indicator level by the corresponding kits using the rat experimental models. Results: Compared with the model group, body weight markedly increased after 3–6 weeks of intragastric administration of Ziyabet tablets ([Formula: see text]), while the water intake significantly decreased in the same period of time ([Formula: see text]). Food intake and fasting blood sugar level also decreased with the high dosage of Ziyabet tablets ([Formula: see text]). There is no significant difference in pancreas’ MDA content of the Ziyabet groups when compared to the model group ([Formula: see text]), while significant increase in SOD level was observed in high-dosage KZ group ([Formula: see text]). The blood serum insulin and free fatty acid level also decreased in the high-dosage KZ group compared with the model group ([Formula: see text]). Conclusion: We conclude that Ziyabet tablets demonstrated protective effects on the diabetic rat models.

scholarly journals Brain Targeting of anti-HIV Nucleosides: in vitro and in vivo Evaluation of 6-chloro-2′,3′-dideoxypurine, a Lipophilic Prodrug of 2′,3′-dideoxyinosine

1994 ◽  
Vol 5 (5) ◽  
pp. 304-311 ◽  
Author(s):  
K. J. Doshi ◽  
F. D. Boudinot ◽  
J. M. Gallo ◽  
R. F. Schinazi ◽  
C. K. Chu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Oral Administration ◽  
Intravenous Administration ◽  
Brain Targeting ◽  
The Central Nervous System ◽  
Intravenous And Oral Administration ◽  
The Brain

Lipophilic 6-halo-2′,3′-dideoxypurine nucleosides may be useful prodrugs for the targeting of 2′,3′-dideoxyinosine (ddl) to the central nervous system. The purpose of this study was to evaluate the potential effectiveness of 6-chloro-2′,3′-dideoxypurine (6-CI-ddP) for the targeting of ddl to the brain. In vitro studies indicated that the adenosine deaminase-mediated biotransformation of 6-CI-ddP to ddl was more rapid in mouse brain homogenate than in mouse serum. The brain distribution of 6-CI-ddP and ddl was assessed in vivo in mice following intravenous and oral administration of the prodrug or parent drug. Brain concentrations of ddl were similar after intravenous administration of 6-CI-ddP or ddl. However, after oral administration of the 6-CI-ddP prodrug, significantly greater concentrations of ddl were seen in the brain compared to those found after oral administration of ddl. The brain:serum AUG ratio (expressed as a percentage) of ddl after intravenous administration of 50 mg kg−1 of the active nucleoside was 3%. Following oral administration of 250 mg kg−1 ddl, low concentrations of ddl were detected in the brain. Brain:serum AUC ratios following intravenous and oral administration of the prodrug 6-CI-ddP were 19–25%. Thus, brain:serum AUC ratios were 6- to 8-fold higher after prodrug administration than those obtained after administration of the parent nucleoside. Oral administration of 6-CI-ddP yielded concentrations of ddl in the brain similar to those obtained following intravenous administration. The results of this study provide further evidence that 6-CI-ddP may be a useful prodrug for delivering ddl to the central nervous system, particularly after oral administration.

scholarly journals Effect of Oral Administration of Butyrivibrio fibrisolvens MDT-1 on Experimental Enterocolitis in Mice

2006 ◽  
Vol 13 (11) ◽  
pp. 1231-1236 ◽  
Author(s):  
Sou Ohkawara ◽  
Hideki Furuya ◽  
Kousuke Nagashima ◽  
Narito Asanuma ◽  
Tsuneo Hino
Keyword(s):  
Body Weight ◽  
Oral Administration ◽  
Body Weight Gain ◽  
Mucosal Damage ◽  
Campylobacter Coli ◽  
Activity Levels ◽  
Bloody Stool ◽  
Colonic Tissue ◽  
Butyrivibrio Fibrisolvens

ABSTRACT Butyrivibrio fibrisolvens MDT-1, a butyrate-producing strain, was evaluated for use as a probiotic to prevent enterocolitis. Oral administration of the MDT-1 strain (109 CFU/dose) alleviated the symptoms of colitis (including body weight loss, diarrhea, bloody stool, organic disorder, and mucosal damage) that are induced in mice drinking water that contains 3.0% dextran sulfate sodium. In addition, myeloperoxidase (MPO) activity levels in colonic tissue were reduced, suggesting that MDT-1 mitigates bowel inflammation. The addition of MDT-1 culture supernatant inhibited the growth of nine clinical isolates of Campylobacter jejuni and Campylobacter coli that could potentially cause enterocolitis. Infection of mice with C. coli 11580-3, one of the isolates inhibited by MDT-1 in vitro, resulted in diarrhea, mucosal damage, increased MPO activity levels in colonic tissue, increased numbers of C. coli in the cecum, and decreased body weight gain. However, administration of MDT-1 to mice, prior to and during C. coli infection, reduced these effects. These results suggest that Campylobacter-induced enterocolitis can be alleviated by using B. fibrisolvens as a probiotic.

scholarly journals Pharmacokinetics of Itraconazole in Diabetic Rats

2009 ◽  
Vol 54 (2) ◽  
pp. 931-933 ◽  
Author(s):  
Unji Lee ◽  
Young H. Choi ◽  
So H. Kim ◽  
Byung K. Lee
Keyword(s):  
Diabetes Mellitus ◽  
Plasma Concentration ◽  
Oral Administration ◽  
Intrinsic Clearance ◽  
Diabetic Rats ◽  
Clearance Rates ◽  
Time Curve ◽  
Concentration Time ◽  
Streptozotocin Induced Diabetes ◽  
Plasma Concentration Time Curve

ABSTRACT After intravenous or oral administration of 10 mg/kg itraconazole to rats with streptozotocin-induced diabetes mellitus and to control rats, the total area under the plasma concentration-time curve from time 0 to 24 h (AUC0-24) for itraconazole and that for its metabolite, 7-hydroxyitraconazole, were similar between the two groups of rats. This may be explained by the comparable hepatic and intestinal intrinsic clearance rates for the disappearance of itraconazole and the formation of 7-hydroxyitraconazole in both groups of rats.

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