Pharmacokinetics of drugs in rats with diabetes mellitus induced by alloxan or streptozocin: comparison with those in patients with type I diabetes mellitus
Identifieur interne : 001684 ( Main/Curation ); précédent : 001683; suivant : 001685Pharmacokinetics of drugs in rats with diabetes mellitus induced by alloxan or streptozocin: comparison with those in patients with type I diabetes mellitus
Auteurs : Joo H. Lee [Corée du Sud] ; Si H. Yang [Corée du Sud] ; Jung M. Oh [Corée du Sud] ; Myung G. Lee [Corée du Sud]Source :
- Journal of Pharmacy and Pharmacology [ 0022-3573 ] ; 2010-01.
English descriptors
- Teeft :
- Acta, Adriamycin, Albino, Alloxan, Amidopyrine, Antibiotic, Atenolol, Azosemide, Biliary, Biliary clearance, Biliary clearance values, Biliary excretion, Biliary excretions, Bilirubin, Biochem, Biochem pharmacol, Biopharm, Biopharm drug dispos, Carbapenem, Cefazolin, Cefoperazone, Cefotaxime, Cefradine, Chlorzoxazone, Choi, Ciclosporin, Clarithromycin, Clearance, Clin, Clin pharmacol, Clnr, Clnr values, Cytochrome, Diabetes, Diabetes mellitus, Diabetes mellitus patients, Diabetes mellitus rats, Diabetic, Diabetic rats, Diclofenac, Different results, Diflunisal, Digoxin, Dispos, Dmia, Dmia rats, Dmis, Dmis rats, Doxorubicin, Drug metab dispos, Enzyme inducers, Excretion, Experimental diabetes, Fenoprofen, Fluorouracil, Free fractions, Furosemide, Glucuronide, Glutathione, Hepatic, Hepatic blood flow rate, Hepatic clint, Hepatic effect, Hepatic extraction ratio, High hepatic extraction ratio, Hydroxychloroquine, Inducer, Intermediate hepatic extraction ratio, Intestinal, Intestine, Intravenous, Intravenous administration, Ipriflavone, Isozyme, Isozymes, Itraconazole, Lidocaine, Liquiritigenin, Liver microsomes, Losartan, Male dmia, Male dmia rats, Male dmis rats, Male rats, Male wistar dmis rats, Mellitus, Metab, Metabolism, Metformin, Microsome, Mirodenafil, Mrna, Mrna level, Mrna levels, Nelfinavir, Oltipraz, Omeprazole, Oral administration, Ouabain, Paeb, Paracetamol, Pathol pharmacol, Pharm, Pharm pharmacol, Pharmacodynamics, Pharmacokinet, Pharmacokinetic, Pharmacokinetic changes, Pharmacokinetic parameters, Pharmacokinetics, Pharmacol, Pharmacology, Phenytoin, Propofol, Protein expression, Rat, Renal, Spraguedawley, Streptozocin, Streptozotocin, Subfamily, Sulfate, Telithromycin, Testis, Testosterone, Theophylline, Torasemide, Tungstate, Unpublished data, Urine, Wistar, Zopolrestat.
Abstract
Objectives In rats with diabetes mellitus induced by alloxan (DMIA) or streptozocin (DMIS), changes in the cytochrome P450 (CYP) isozymes in the liver, lung, kidney, intestine, brain, and testis have been reported based on Western blot analysis, Northern blot analysis, and various enzyme activities. Changes in phase II enzyme activities have been reported also. Hence, in this review, changes in the pharmacokinetics of drugs that were mainly conjugated and metabolized via CYPs or phase II isozymes in rats with DMIA or DMIS, as reported in various literature, have been explained. The changes in the pharmacokinetics of drugs that were mainly conjugated and mainly metabolized in the kidney, and that were excreted mainly via the kidney or bile in DMIA or DMIS rats were reviewed also. For drugs mainly metabolized via hepatic CYP isozymes, the changes in the total area under the plasma concentration–time curve from time zero to time infinity (AUC) of metabolites, AUCmetabolite/AUCparent drug ratios, or the time‐averaged nonrenal and total body clearances (CLNR and CL, respectively) of parent drugs as reported in the literature have been compared. Key findings After intravenous administration of drugs that were mainly metabolized via hepatic CYP isozymes, their hepatic clearances were found to be dependent on the in‐vitro hepatic intrinsic clearance (CLint) for the disappearance of the parent drug (or in the formation of the metabolite), the free fractions of the drugs in the plasma, or the hepatic blood flow rate depending on their hepatic extraction ratios. The changes in the pharmacokinetics of drugs that were mainly conjugated and mainly metabolized via the kidney in DMIA or DMIS rats were dependent on the drugs. However, the biliary or renal CL values of drugs that were mainly excreted via the kidney or bile in DMIA or DMIS rats were faster. Summary Pharmacokinetic studies of drugs in patients with type I diabetes mellitus were scarce. Moreover, similar and different results for drug pharmacokinetics were obtained between diabetic rats and patients with type I diabetes mellitus. Thus, present experimental rat data should be extrapolated carefully in humans.
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DOI: 10.1211/jpp.62.01.0001
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<profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Acta</term>
<term>Adriamycin</term>
<term>Albino</term>
<term>Alloxan</term>
<term>Amidopyrine</term>
<term>Antibiotic</term>
<term>Atenolol</term>
<term>Azosemide</term>
<term>Biliary</term>
<term>Biliary clearance</term>
<term>Biliary clearance values</term>
<term>Biliary excretion</term>
<term>Biliary excretions</term>
<term>Bilirubin</term>
<term>Biochem</term>
<term>Biochem pharmacol</term>
<term>Biopharm</term>
<term>Biopharm drug dispos</term>
<term>Carbapenem</term>
<term>Cefazolin</term>
<term>Cefoperazone</term>
<term>Cefotaxime</term>
<term>Cefradine</term>
<term>Chlorzoxazone</term>
<term>Choi</term>
<term>Ciclosporin</term>
<term>Clarithromycin</term>
<term>Clearance</term>
<term>Clin</term>
<term>Clin pharmacol</term>
<term>Clnr</term>
<term>Clnr values</term>
<term>Cytochrome</term>
<term>Diabetes</term>
<term>Diabetes mellitus</term>
<term>Diabetes mellitus patients</term>
<term>Diabetes mellitus rats</term>
<term>Diabetic</term>
<term>Diabetic rats</term>
<term>Diclofenac</term>
<term>Different results</term>
<term>Diflunisal</term>
<term>Digoxin</term>
<term>Dispos</term>
<term>Dmia</term>
<term>Dmia rats</term>
<term>Dmis</term>
<term>Dmis rats</term>
<term>Doxorubicin</term>
<term>Drug metab dispos</term>
<term>Enzyme inducers</term>
<term>Excretion</term>
<term>Experimental diabetes</term>
<term>Fenoprofen</term>
<term>Fluorouracil</term>
<term>Free fractions</term>
<term>Furosemide</term>
<term>Glucuronide</term>
<term>Glutathione</term>
<term>Hepatic</term>
<term>Hepatic blood flow rate</term>
<term>Hepatic clint</term>
<term>Hepatic effect</term>
<term>Hepatic extraction ratio</term>
<term>High hepatic extraction ratio</term>
<term>Hydroxychloroquine</term>
<term>Inducer</term>
<term>Intermediate hepatic extraction ratio</term>
<term>Intestinal</term>
<term>Intestine</term>
<term>Intravenous</term>
<term>Intravenous administration</term>
<term>Ipriflavone</term>
<term>Isozyme</term>
<term>Isozymes</term>
<term>Itraconazole</term>
<term>Lidocaine</term>
<term>Liquiritigenin</term>
<term>Liver microsomes</term>
<term>Losartan</term>
<term>Male dmia</term>
<term>Male dmia rats</term>
<term>Male dmis rats</term>
<term>Male rats</term>
<term>Male wistar dmis rats</term>
<term>Mellitus</term>
<term>Metab</term>
<term>Metabolism</term>
<term>Metformin</term>
<term>Microsome</term>
<term>Mirodenafil</term>
<term>Mrna</term>
<term>Mrna level</term>
<term>Mrna levels</term>
<term>Nelfinavir</term>
<term>Oltipraz</term>
<term>Omeprazole</term>
<term>Oral administration</term>
<term>Ouabain</term>
<term>Paeb</term>
<term>Paracetamol</term>
<term>Pathol pharmacol</term>
<term>Pharm</term>
<term>Pharm pharmacol</term>
<term>Pharmacodynamics</term>
<term>Pharmacokinet</term>
<term>Pharmacokinetic</term>
<term>Pharmacokinetic changes</term>
<term>Pharmacokinetic parameters</term>
<term>Pharmacokinetics</term>
<term>Pharmacol</term>
<term>Pharmacology</term>
<term>Phenytoin</term>
<term>Propofol</term>
<term>Protein expression</term>
<term>Rat</term>
<term>Renal</term>
<term>Spraguedawley</term>
<term>Streptozocin</term>
<term>Streptozotocin</term>
<term>Subfamily</term>
<term>Sulfate</term>
<term>Telithromycin</term>
<term>Testis</term>
<term>Testosterone</term>
<term>Theophylline</term>
<term>Torasemide</term>
<term>Tungstate</term>
<term>Unpublished data</term>
<term>Urine</term>
<term>Wistar</term>
<term>Zopolrestat</term>
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<front><div type="abstract" xml:lang="en">Objectives In rats with diabetes mellitus induced by alloxan (DMIA) or streptozocin (DMIS), changes in the cytochrome P450 (CYP) isozymes in the liver, lung, kidney, intestine, brain, and testis have been reported based on Western blot analysis, Northern blot analysis, and various enzyme activities. Changes in phase II enzyme activities have been reported also. Hence, in this review, changes in the pharmacokinetics of drugs that were mainly conjugated and metabolized via CYPs or phase II isozymes in rats with DMIA or DMIS, as reported in various literature, have been explained. The changes in the pharmacokinetics of drugs that were mainly conjugated and mainly metabolized in the kidney, and that were excreted mainly via the kidney or bile in DMIA or DMIS rats were reviewed also. For drugs mainly metabolized via hepatic CYP isozymes, the changes in the total area under the plasma concentration–time curve from time zero to time infinity (AUC) of metabolites, AUCmetabolite/AUCparent drug ratios, or the time‐averaged nonrenal and total body clearances (CLNR and CL, respectively) of parent drugs as reported in the literature have been compared. Key findings After intravenous administration of drugs that were mainly metabolized via hepatic CYP isozymes, their hepatic clearances were found to be dependent on the in‐vitro hepatic intrinsic clearance (CLint) for the disappearance of the parent drug (or in the formation of the metabolite), the free fractions of the drugs in the plasma, or the hepatic blood flow rate depending on their hepatic extraction ratios. The changes in the pharmacokinetics of drugs that were mainly conjugated and mainly metabolized via the kidney in DMIA or DMIS rats were dependent on the drugs. However, the biliary or renal CL values of drugs that were mainly excreted via the kidney or bile in DMIA or DMIS rats were faster. Summary Pharmacokinetic studies of drugs in patients with type I diabetes mellitus were scarce. Moreover, similar and different results for drug pharmacokinetics were obtained between diabetic rats and patients with type I diabetes mellitus. Thus, present experimental rat data should be extrapolated carefully in humans.</div>
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