Effect of a newly developed ketolide antibiotic, telithromycin, on metabolism of theophylline and expression of cytochrome P450 in rats

Nosaka, Hiroyuki; Nadai, Masayuki; Kato, Mayumi; Yasui, Kazumasa; Yoshizumi, Hajime; Miyoshi, Mika; Zhao, Ying; Baba, Kenji; Takagi, Kenzo; Hasegawa, Takaaki

doi:10.1016/j.lfs.2005.12.022

Cited by 14 publications

(8 citation statements)

References 32 publications

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“…The values of the pharmacokinetic parameters and urinary recovery of theophylline and its metabolites observed in control rats were comparable to those of our previous studies. 12,29) Unexpectedly, results obtained from the present study showed that neither single intravenous injection nor multiple intraperitoneal injections of aciclovir altered the plasma concentration-time profiles and pharmacokinetic parameters of theophylline. In addition, aciclovir had no effect on the urinary recovery of theophylline metabolites, 1-methyluric acid and 1,3-dimethyluric acid, during a urine collection period of 24 h, which is about 7-fold longer than the plasma half-life of theophylline (approximately 3 h), although slight increases in the urinary recovery of the two metabolites were observed in rats treated with multiple intraperitoneal injections of aciclovir.…”

Section: Discussioncontrasting

confidence: 48%

“…However, our previous experiments using rats demonstrated that enoxacin significantly decreased the systemic clearance of theophylline by inhibiting hepatic metabolism and that telithromycin significantly inhibited the theophylline metabolism by decreasing the activity and expression of hepatic CYP1A2. 12,29) Based on these results, the present study, at least, suggests that the inhibitory effect of aciclovir against CYP1A2 is weaker than these drugs in rats.…”

Section: Discussionmentioning

confidence: 51%

“…3,4) Many articles have been published on the drug interactions of theophylline with other coadministered drugs mediated by cytochrome P450 (CYP) 1A2, which is the major metabolizing enzyme for theophylline. [5][6][7][8][9][10][11][12] For example, it is well known that histamine H 2 -antagonist cimetidine and quinolone antimicrobial agent enoxacin cause the risk of the development of serious side effects by inhibiting CYP1A2-mediated theophylline metabolism in the liver. 7,9,13,14) The antivirus agent aciclovir, which has potent inhibitory activity against herpes simplex virus and varicella zoster virus, [15][16][17] is known to be mainly eliminated from the kidney.…”

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confidence: 99%

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Lack of Effect of Aciclovir on Metabolism of Theophylline and Expression of Hepatic Cytochrome P450 1A2 in Rats

Nadai

Kato

Yasui

et al. 2007

Biological & Pharmaceutical Bulletin

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Theophylline is widely used in the treatment of patients with obstructive airway diseases. It is well known that theophylline has a narrow therapeutic range being a plasma concentration of 10-20 mg/ml 1,2) and is extensively metabolized in humans. 3,4) Many articles have been published on the drug interactions of theophylline with other coadministered drugs mediated by cytochrome P450 (CYP) 1A2, which is the major metabolizing enzyme for theophylline. [5][6][7][8][9][10][11][12] For example, it is well known that histamine H 2 -antagonist cimetidine and quinolone antimicrobial agent enoxacin cause the risk of the development of serious side effects by inhibiting CYP1A2-mediated theophylline metabolism in the liver. 7,9,13,14) The antivirus agent aciclovir, which has potent inhibitory activity against herpes simplex virus and varicella zoster virus, [15][16][17] is known to be mainly eliminated from the kidney. 18,19) Drug interaction between aciclovir and concomitantly administered drugs, such as cimetidine, probenecid and mycophenolate that are primarily excreted into the urine has been reported. [20][21][22] However, there is an interesting clinical report indicating that total body clearance of theophylline is decreased by multiple oral administrations of aciclovir (800 mg five times daily for two consecutive days) in healthy volunteers, 23) although theophylline is extensively metabolized in the liver. They proposed that the mechanism responsible for the decreases in theophylline clearance by coadministration of aciclovir might be due to inhibition of CYP1A2-mediated theophylline metabolism. However, the effect of aciclovir on the activity and expression of CYP1A2 remains unclear.We have previously reported that rats are a useful animal model for predicting drug interaction between theophylline and other drugs in humans. [24][25][26][27][28][29] The aim of the present study was to investigate the effect of aciclovir on the pharmacokinetics and metabolism of theophylline, and on the activity and expression of hepatic CYP1A2 in rats. To further clarify whether aciclovir has an inhibitory effect against hepatic CYP1A2, we also investigated the effect of aciclovir on the pharmacokinetics of the xanthine derivative 1-methyl-3-propylxanthine, which is almost completely metabolized by CYP1A2 in rats. 29,30) MATERIALS AND METHODS Chemicals Theophylline, aciclovir, resorufin and 7-ethoxyresorufin were purchased from Sigma Chemical Company (St. Louis, MO, U.S.A.). Aciclovir in the form of a commercial preparation for injection (Zovirax for IV infusion) was obtained from GlaxoSmithKline K.K. (Tokyo, Japan). Enprofylline, 1-methyl-3-propylxanthine and 1-methyl-3-buthylxanthine were synthesized in our laboratory and were identical to those previously described.29,31) Enprofylline and 1-methyl-3-buthylxanthine were used as internal standards for determination of concentrations of theophylline and 1-methyl-3-propylxanthine, respectively. Inulin was purchased from Nacalai Tesque (Kyoto, Japan). All other There is an interes...

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Section: Discussioncontrasting

confidence: 48%

Section: Discussionmentioning

confidence: 51%

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confidence: 99%

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Lack of Effect of Aciclovir on Metabolism of Theophylline and Expression of Hepatic Cytochrome P450 1A2 in Rats

Nadai

Kato

Yasui

et al. 2007

Biological & Pharmaceutical Bulletin

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“…Thus, ketolides have a high potential for clinically significant drug-drug interactions. In addition, they (telithromycin) decrease protein levels, and thereby activity, of CYP1A2 and CYP3A2, the result being decreased metabolic clearance of the common asthma drug theophylline [50].…”

Section: Pharmacokinetics Metabolism Clinical Trialsmentioning

confidence: 99%

The wobbly status of ketolides: where do we stand?

Georgopapadakou¹

2014

Expert Opinion on Investigational Drugs

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“…For example, telithromycin has been reported to be a potent inhibitor of CYP3A4 and thus interfere with the pharmacokinetics of many other drugs that are metabolized by this enzyme (Shakeri-Nejad & Stahlmann 2006). A significant decrease in the metabolic clearance of theophylline was observed in the presence of telithromycin in rats due to the reductions in the activity and expression of hepatic CYP1A2 and CYP3A2 (Nosaka et al 2006). Competitive inhibition between DA-8159 and metformin via CYP3A1/2 (Choi et al 2008a) and between nifedipine and metformin via CYP3A1 and 2C11 (Choi 2008) have also been reported in rats.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic interaction between telithromycin and metformin in diabetes mellitus rats

2009

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Telithromycin and metformin have been reported to be commonly metabolized via hepatic CYP3A1/2 in rats. Community-acquired respiratory tract infection was reported to be frequent in patients with diabetes mellitus. Compared with controls, hepatic CYP3A1/2 was reported to be increased in male rats with diabetes mellitus induced by streptozotocin (DMIS rats). After the intravenous administration of both drugs together to male DMIS rats, the time-averaged non-renal clearance (CL(NR)) of metformin was significantly slower (by 33.1%; 10.3 versus 15.4 ml min(-1) kg(-1)) than metformin alone due to the inhibition of hepatic metabolism of metformin by telithromycin via CYP3A1/2. After the oral administration of both drugs together, the total area under the plasma concentration-time curve (AUC) of metformin was comparable possibly due to the increased intestinal metabolism of metformin by telithromycin.

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Effect of a newly developed ketolide antibiotic, telithromycin, on metabolism of theophylline and expression of cytochrome P450 in rats

Cited by 14 publications

References 32 publications

Lack of Effect of Aciclovir on Metabolism of Theophylline and Expression of Hepatic Cytochrome P450 1A2 in Rats

Lack of Effect of Aciclovir on Metabolism of Theophylline and Expression of Hepatic Cytochrome P450 1A2 in Rats

The wobbly status of ketolides: where do we stand?

Pharmacokinetic interaction between telithromycin and metformin in diabetes mellitus rats

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