Pharmacokinetics of a new carbapenem, DA-1131, after intravenous administration to rats with alloxan-induced diabetes mellitus

Kim, So H.; Kim, Won B.; Lee, Myung G.

doi:10.1002/(sici)1099-081x(199807)19:5<303::aid-bdd103>3.0.co;2-5

Cited by 19 publications

(23 citation statements)

References 6 publications

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“…Similar results were also reported elsewhere (Kim et al, 1998). The plasma levels of AST (66.9% increase) and insulin (36.4% increase) were significantly higher in ARF rats than those in control rats (Table 1).…”

Section: Induction Of Arfmentioning

confidence: 99%

Increase in Urea in Conjunction with l-Arginine Metabolism in the Liver Leads to Induction of Cytochrome P450 2E1 (CYP2E1): The Role of Urea in CYP2E1 Induction by Acute Renal Failure

Chung

Kim²,

Lee³

et al. 2002

Drug Metab Dispos

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ABSTRACT:A number of xenobiotics and certain pathophysiological situations cause the induction of CYP2E1. The present study was designed to establish the role of plasma urea nitrogen and L-arginine on hepatic CYP2E1 expression in rats or rats with acute renal failure. Exposure of rats to a single intravenous dose of 5 mg/kg uranyl nitrate caused renal failure in 5 days (ARF), as evidenced by increases in plasma urea nitrogen level and kidney to body weight ratio. Northern and Western blot analyses revealed that hepatic CYP2E1 was 2-to 4-fold induced by ARF. Treatment of rats with either 10% glucose in drinking water for 5 days following a single injection of uranyl nitrate or two injections of recombinant growth hormone (5 units/kg, s.c., twice a day) on the 4th day after uranyl nitrate injection reduced both the rise in plasma urea nitrogen and the induction of CYP2E1. Exposure of rats to urea (ϳ225 mg/kg/ day) in drinking water for 1 to 3 day(s) resulted in significant increases in CYP2E1 mRNA and protein. Furthermore, perfusion of the liver with 25 mM urea for 24 h resulted in CYP2E1 induction with an increase in the mRNA. The levels of CYP2E1 protein and mRNA were increased in rats perfused with 25 mM L-arginine for 24 h (i.e., a 4-fold increase). Hence, L-arginine, which is irreversibly hydrolyzed to urea and ornithine by arginase, also induced hepatic CYP2E1. The results of the present study provided evidence that increases in plasma urea in conjunction with L-arginine metabolism lead to the induction of CYP2E1 in the liver.

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Section: Induction Of Arfmentioning

confidence: 99%

Increase in Urea in Conjunction with l-Arginine Metabolism in the Liver Leads to Induction of Cytochrome P450 2E1 (CYP2E1): The Role of Urea in CYP2E1 Induction by Acute Renal Failure

Chung

Kim²,

Lee³

et al. 2002

Drug Metab Dispos

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“…Glucuronidation and sulfation were also profoundly affected by DMIS in rats (23). In rats with diabetes mellitus induced by alloxan (DMIA), kidney function was also impaired (12,20).A previous study (13) has shown that the expression of hepatic microsomal cytochrome P450 (CYP) 1A2, 2B1/2, 2E1, and 3A23 increased 2.8, 1.8, 3.0, and 1.5 times, respectively, in rats with DMIA compared to controls, whereas the expression of CYP2C11 decreased to 23% of the control value. Similarly, the expression of CYP1A2, 2B1/2, 2E1, and 3A23 also increased 3.1, 3.3, 2.8, and 1.9 times, respectively, in rats with DMIS compared to controls, whereas the expression of CYP2C11 decreased to 37% of the control value.…”

mentioning

confidence: 99%

“…Glucuronidation and sulfation were also profoundly affected by DMIS in rats (23). In rats with diabetes mellitus induced by alloxan (DMIA), kidney function was also impaired (12,20).…”

mentioning

confidence: 99%

“…Chemicals (1,14), the methods of induction of diabetes mellitus by alloxan (12,20) or streptozotocin (21), pretreatment and surgical procedures for intravenous and oral administration (1, 14), procedures for intravenous (n ϭ 12 and 11 for rats with DMIA and their control rats, respectively, and n ϭ 8 and 7 for rats with DMIS and their control rats, respectively) and oral (n ϭ 9 and 11 for rats with DMIA and their control rats, respectively, and n ϭ 10 and 9 for rats with DMIS and their control rats, respectively) studies (1,14), and high-performance liquid chromatography analysis of clarithromycin (1,14) were similar to previously reported methods. The procedures for the measurement of the maximum rate of metabolism (V max ), K m , and the intrinsic clearance (CL int ) for the disappearance of clarithromycin in hepatic microsomal fractions were similar to previously reported methods (1).…”

mentioning

confidence: 99%

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

Kim

Lee

Kim

et al. 2005

Antimicrob Agents Chemother

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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.Animal models of insulin-dependent diabetes mellitus induced by administration of several chemicals, principally alloxan, streptozotocin, and zinc chelators, have been reported (22, 30). There are major differences in the diabetic effects of streptozotocin and alloxan (reference 30 and references therein). It is known that structural alterations in pancreatic beta cells (total degranulation) occur within 48 h after administration of streptozotocin and last up to 4 months. Alloxan causes a decrease in hepatic glycogen within 24 to 72 h, an effect that is partially reversible by insulin. Alloxan generally produces greater cytotoxicity owing to its conversion to anionic radicals.For rats with diabetes mellitus induced by streptozotocin (DMIS), a decreased bile flow rate and altered bile compositions (3), hepatotoxicity (31), and impaired kidney function (18, 21) have been reported. Glucuronidation and sulfation were also profoundly affected by DMIS in rats (23). In rats with diabetes mellitus induced by alloxan (DMIA), kidney function was also impaired (12,20).A previous study (13) has shown that the expression of hepatic microsomal cytochrome P450 (CYP) 1A2, 2B1/2, 2E1, and 3A23 increased 2.8, 1.8, 3.0, and 1.5 times, respectively, in rats with DMIA compared to controls, whereas the expression of CYP2C11 decreased to 23% of the control value. Similarly, the expression of CYP1A2, 2B1/2, 2E1, and 3A23 also increased 3.1, 3.3, 2.8, and 1.9 times, respectively, in rats with DMIS compared to controls, whereas the expression of CYP2C11 decreased to 37% of the control value. The mRNA levels of CYP1A2, 2B1, 2B2, 2E1, and 3A23 increased 3.4, 1.9, 1.6, 4.3, and 1.6 times, respectively, in rats with DMIA compared to controls, whereas CYP2C11 decreased to 31% of the control value. Similarly, the mRNA levels of CYP1A2, 2B1, 2B2, 2E1, and 3A23 also increased 4.2, 3.9, 1.9, 3.6, and 2.2 times, respectively, in rats with DMIS compared to controls, whereas CYP2C11 decreased to 28% of the control value. Similar changes in some of the above-mentioned CYP isozymes have also been reported for rats with DMIA and/or DMIS (8,15,(24)(25)(26)(27)32).It has been reported that CYP3A1 (23) is involved in the metabolism of clarithromycin in rats (14). Hence, it would be expected that pharmacokinetics of clarithromycin could be changed in rats with DMIA and DMIS due to an increase in the expression and...

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“…DA (10,12,13,16,17,18,19), in the renal excretion mechanism (14,15), and in nephrotoxicity-related studies (11).…”

Section: Imipenem (N-formimidoylthienamycin) Developed By Merckmentioning

confidence: 99%

Stability of New Carbapenem DA-1131 to Renal Dipeptidase (Dehydropeptidase I)

Park

Kim

et al. 2002

Antimicrob Agents Chemother

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The stability of DA-1131 to renal dipeptidase (RDPase) (EC 3.4.13.19) was compared with that of imipenem and meropenem by V max /K m ratios as an index of the enzyme's preference for substrates. Our results showed a decreasing order of imipenem (6.24), meropenem (2.41), and DA-1131 (1.39). The biochemical evaluation of DA-1131 as the least preferred substrate of RDPase suggests its potential use as a novel ␤-lactam antibiotic which may be usable without coadministration of RDPase inhibitors once its clinical suitability is proven.Imipenem (N-formimidoylthienamycin), developed by Merck Sharp & Dohme, West Point, Pa., was highly effective against bacterial species resistant to most ␤-lactam antibiotics with unusually high potency against gram-positive as well as gramnegative bacteria (8,21,23). It is degraded, though, in the kidneys of various animals, resulting in a reduced antibacterial activity. The enzyme responsible for this metabolism was shown to be renal dipeptidase (RDPase, also called renal dehydropeptidase I) (EC 3.4.13.19) located in the brush-border membrane of renal proximal tubules (8,9,20). Cilastatin, Z-2-(2,2-dimethylcyclopropanecarboxamido)-2-butenoic acid, is a specific competitive inhibitor of RDPase and is well matched in its pharmacokinetic properties for coadministration with imipenem (8,22). Therefore, imipenem is designed to be coadministered with cilastatin to suppress RDPase for its clinical use, and they are now manufactured in a 1:1 combination.Meropenemhept-2-ene-2-carboxylic acid, which was introduced in the late 1980s, though relatively less active against gram-positive bacteria than imipenem (1,4,6,7), is stable in the presence of RDPase as judged by its V max /K m ratio. Thus, it is currently in clinical use without coadministration of an RDPase inhibitor.DA 237, 1996). DA-1131 has been examined in many aspects, including pharmacokinetics under various conditions in animals (10,12,13,16,17,18,19), in the renal excretion mechanism (14, 15), and in nephrotoxicity-related studies (11).We measured the kinetic parameters of imipenem, meropenem, and DA-1131 in relation to human RDPase and the RDPases of various animals to examine the stability of DA-1131 in reference to the two well-established ␤-lactam antibiotics, imipenem and meropenem.DA-1131 and meropenem were supplied by Dong-A Research Laboratory. Imipenem and cilastatin were obtained from Merck Sharp & Dohme. Human RDPase was purified to homogeneity with a 2,029-fold purification, and RDPases from animal sources were purified or partially purified according to the method previously described (24).RDPase-catalyzed hydrolysis of imipenem, meropenem, and DA-1131 was measured in the presence and absence of cilastatin (0.15 M) according to the method described by Kim and Campbell (9) by measuring the decrease in absorbance at 298 nm and 37°C as a function of time for 2.5 min. Substrate concentration was varied over a range of 1.25 to 3.3 mM in 3-(N-morpholino)propanesulfonic acid, pH 7.1. One microgram of purified RDPase was employ...

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Pharmacokinetics of a new carbapenem, DA-1131, after intravenous administration to rats with alloxan-induced diabetes mellitus

Cited by 19 publications

References 6 publications

Increase in Urea in Conjunction with l-Arginine Metabolism in the Liver Leads to Induction of Cytochrome P450 2E1 (CYP2E1): The Role of Urea in CYP2E1 Induction by Acute Renal Failure

Increase in Urea in Conjunction with l-Arginine Metabolism in the Liver Leads to Induction of Cytochrome P450 2E1 (CYP2E1): The Role of Urea in CYP2E1 Induction by Acute Renal Failure

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

Stability of New Carbapenem DA-1131 to Renal Dipeptidase (Dehydropeptidase I)

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