Comparative pharmacokinetics of clarithromycin (TE-031), a new macrolide antibiotic, and erythromycin in rats

Kohno, Yoshiro; Yoshida, Hideo; Suwa, Toshio; Suga, Tetsuya

doi:10.1128/aac.33.5.751

Cited by 45 publications

(18 citation statements)

References 6 publications

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“…Clarithromycin has been shown to achieve higher levels than erythromycin in the lungs of rodents [4]. Azithromycin [16] has also been found to be concentrated in lung tissues.…”

Section: Discussionmentioning

confidence: 99%

“…There is some evidence to suggest a possible synergy between clarithromycin and its 14-hydroxy metabolite, which may be of relevance for some infections [3]. Clarithromycin serum half-life is longer than erythromycin, and some studies have suggested tissue concentrations to be higher after oral clarithromycin than after oral erythromycin [4]. Macrolides are known to accumulate within cells, including neutrophils and macrophages [5].…”

mentioning

confidence: 99%

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The levels of clarithromycin and its 14-hydroxy metabolite in the lung

Honeybourne¹,

Kees²,

Andrews³

et al. 1994

Eur Respir J

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T Th he e l le ev ve el ls s o of f c cl la ar ri it th hr ro om my yc ci in n a an nd d i it ts s 1 14 4--h hy yd dr ro ox xy y m me et ta ab bo ol li it te e i in n t th he e l lu un ng g ABSTRACT: Clarithromycin is a new macrolide that has a longer half-life than erythromycin and is claimed to reach higher tissue concentrations. We aimed to investigate whether, following oral administration, the drug and its 14-hydroxy metabolite reach levels in lung tissue that are likely to be clinically effective against common respiratory pathogens. Ten patients undergoing diagnostic bronchoscopy received seven doses of clarithromycin, 500 mg b.i.d. orally. Bronchoscopy was performed at a mean time of 4.25 h after the last dose. At bronchoscopy, bronchial biopsies and bronchoalveolar lavage were performed. Clarithromycin and its 14-OH metabolite were measured in serum, bronchial biopsies, epithelial lining fluid (ELF) and alveolar cells.Mean levels of clarithromycin were 4.0 mg·l -1 in serum, 16.8 mg·kg in bronchial biopsies, 20.5 mg·l -1 in ELF and 372.7 mg·l -1 in alveolar cells. The equivalent levels of 14-OH metabolite were 0.7, 2.7, 1.9 and 38.6 mg·l -1 , respectively.We conclude that there is considerable concentration of clarithromycin and its 14-OH metabolite in alveolar cells, and to a lesser extent in bronchial tissue and ELF; this implies efficacy against susceptible organisms at these sites.

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“…Clarithromycin has been shown to achieve higher levels than erythromycin in the lungs of rodents [4]. Azithromycin [16] has also been found to be concentrated in lung tissues.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The levels of clarithromycin and its 14-hydroxy metabolite in the lung

Honeybourne¹,

Kees²,

Andrews³

et al. 1994

Eur Respir J

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“…It is primarily metabolized to its biologically active 14-hydroxyclarithromycin. 63,64) The compound has demonstrated excellent in vitro activity against Legionella species than erythromycin. The activity of 14-hydroxyclarithromycin against penicillin-intermediate, penicillin-resistant or erythromycin-resistant Streptococcus pneumoniae was approximately a half of that of parent drug.…”

Section: Citaloprammentioning

confidence: 99%

Pharmacologically Active Metabolites of Currently Marketed Drugs: Potential Resources for New Drug Discovery and Development

et al. 2010

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Biotransformation is the major clearance mechanism of therapeutic agents from the body. Biotransformation is known not only to facilitate the elimination of drugs by changing the molecular structure to more hydrophilic, but also lead to pharmacological inactivation of therapeutic compounds. However, in some cases, the biotransformation of drugs can lead to the generation of pharmacologically active metabolites, responsible for the pharmacological actions. This review provides an update of the kinds of pharmacologically active metabolites and some of their individual pharmacological and pharmacokinetic aspects, and describes their importance as resources for drug discovery and development.

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“…It is relatively stable in the presence of gastric acid (15) and has a high affinity for tissue (10). The penicillin antibiotic amoxicillin (AMZ) also has strong in vitro activity against H. pylori (7) and is more stable than macrolides in gastric acid.…”

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confidence: 99%

Effects of Lansoprazole and Amoxicillin on Uptake of [ ¹⁴ C]Clarithromycin into Gastric Tissue in Rats

Endo

Yoshida

Ohmi

et al. 2001

Antimicrob Agents Chemother

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Triple therapy consisting of clarithromycin (CLR), lansoprazole (LPZ), and amoxicillin (AMZ) is effective as eradication therapy for patients with peptic ulcer disease andThe association between active gastritis and Helicobacter pylori was first reported by Warren (24) and Marshall (13), and H. pylori-associated gastritis may be the cause of gastric ulcer. Recently, clinical trials involving the use of antibiotics yielded evidence that antibiotics can eradicate H. pylori (5,6,8,17).The macrolide antibiotic clarithromycin (CLR) is, to date, one of the most active antimicrobial agents against H. pylori in vitro (4). It is relatively stable in the presence of gastric acid (15) and has a high affinity for tissue (10). The penicillin antibiotic amoxicillin (AMZ) also has strong in vitro activity against H. pylori (7) and is more stable than macrolides in gastric acid. Treatment with CLR or AMZ alone in vivo, however, is rarely effective. The eradication rate was 15 to 54% when CLR was administered alone (18) and 20 to 30% when AMZ was administered alone (7). The activities of both CLR and AMZ against H. pylori are affected by pH, as the activities are reduced under acidic conditions (1, 4) and the levels of distribution of the drugs to the gastric mucus and mucosa inhabited by H. pylori are insufficient. When a single antibiotic, CLR or AMZ, was combined with a proton pump inhibitor (lansoprazole [LPZ]) (19), the eradication rates were 57 to 77% (20, 23). H. pylori was eradicated from 84 to 95% of patients concomitantly prescribed LPZ, CLR, and AMZ (2,11,20).To better comprehend the synergism, the effects of LPZ and AMZ on the distribution of 14 C-labeled CLR in rats were investigated, with particular focus on the ability of CLR to penetrate gastric tissue.

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Comparative pharmacokinetics of clarithromycin (TE-031), a new macrolide antibiotic, and erythromycin in rats

Abstract: Clarithromycin (TE-031) is a newly synthesized macrolide with high stability in acidic conditions. In the present study, the pharmacokinetics of [N-methyl-14C]

Cited by 45 publications

References 6 publications

The levels of clarithromycin and its 14-hydroxy metabolite in the lung

The levels of clarithromycin and its 14-hydroxy metabolite in the lung

Pharmacologically Active Metabolites of Currently Marketed Drugs: Potential Resources for New Drug Discovery and Development

Effects of Lansoprazole and Amoxicillin on Uptake of [ ¹⁴ C]Clarithromycin into Gastric Tissue in Rats

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Comparative pharmacokinetics of clarithromycin (TE-031), a new macrolide antibiotic, and erythromycin in rats

Abstract: Clarithromycin (TE-031) is a newly synthesized macrolide with high stability in acidic conditions. In the present study, the pharmacokinetics of [N-methyl-14C]

Cited by 45 publications

References 6 publications

The levels of clarithromycin and its 14-hydroxy metabolite in the lung

The levels of clarithromycin and its 14-hydroxy metabolite in the lung

Pharmacologically Active Metabolites of Currently Marketed Drugs: Potential Resources for New Drug Discovery and Development

Effects of Lansoprazole and Amoxicillin on Uptake of [ 14 C]Clarithromycin into Gastric Tissue in Rats

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Effects of Lansoprazole and Amoxicillin on Uptake of [ ¹⁴ C]Clarithromycin into Gastric Tissue in Rats