Pharmacokinetic Considerations in the Eradication of Helicobacter Pylori

Klotz, Ulrich

doi:10.2165/00003088-200038030-00004

Cited by 103 publications

(93 citation statements)

References 201 publications

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“…In addition to data on total bismuth uptake and elimination, which basically confirmed the results of previous studies on bismuth biodisposition (Slikkerveer and de Wolff, 1989;Klotz, 2000;Sun et al, 2004), data on the identification and quantification of (CH 3 ) 3 Bi in blood and exhaled air samples are given.…”

Section: Discussionsupporting

confidence: 86%

Determination of Trimethylbismuth in the Human Body after Ingestion of Colloidal Bismuth Subcitrate

Boertz¹,

Hartmann²,

Sułkowski³

et al. 2008

Drug Metab Dispos

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ABSTRACT:Biological methylation and hydride formation of metals and metalloids are ubiquitous environmental processes that can lead to the formation of chemical species with significantly increased mobility and toxicity. Whereas much is known about the interaction of metal(loid)s with microorganisms in environmental settings, little information has been gathered on respective processes inside the human body as yet. Here, we studied the biotransformation and excretion of bismuth after ingestion of colloidal bismuth subcitrate (215 mg of bismuth) to 20 male human volunteers. Bismuth absorption in the stomach and upper intestine was very low, as evidenced by the small quantity of bismuth eliminated via the renal route. Total bismuth concentrations in blood increased rapidly in the first hour after ingestion. Most of the ingested bismuth was excreted via feces during the study period. Trace levels of the metabolite trimethylbismuth [(CH 3 ) 3 Bi] were detected via low temperaturegas chromatography/inductively coupled plasma-mass spectrometry in blood samples and in exhaled air samples. Concentrations were in the range of up to 2.50 pg/ml (blood) and 0.8 to 458 ng/m 3 (exhaled air), with high interindividual variation being observed. Elimination routes of bismuth were exhaled air (up to 0.03‰), urine (0.03-1.2%), and feces. The site of (CH 3 ) 3 Bi production could not be identified in the present study, but the intestinal microflora seems to be involved in this biotransformation if accompanying ex vivo studies are taken into consideration.It is a well known fact that the toxicity of metal(loid)s is essentially dependent on the chemical form, i.e., on the species of the element in question (Craig, 2003;Dopp et al., 2004; Hirner and Emons, 2004). In particular, alkylation often seems to considerably increase the toxic potential of metal(loid)s. Many studies have shown that in the environment methylated and also, in some cases, hydride species can be formed by different mechanisms and from a variety of metal(loid)s (Craig, 2003). In particular, microorganisms, e.g., bacteria and fungi, have been reported to be involved in this specific kind of conversion (Thayer, 2002).In contrast to the considerable knowledge that has accumulated on the interaction of microorganisms with metal(loid)s in the environment, a paucity of information is currently available on the respective processes inside the human body. This lack of knowledge is particularly striking in view of the fact that certain segments of the digestive tract, namely, the oral cavity and the colon, are colonized by myriads of bacteria. The difficulty of analyzing metal(loid) organic compounds at trace and even ultratrace levels might at least partly account for this information gap.After a pilot study with three volunteers , we performed an ingestion experiment with bismuth, administering this element as a single p.o. dose to 20 male volunteers in the form of a therapeutically used colloidal bismuth subcitrate compound. Bismuth was chosen as the element of interest ...

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Section: Discussionsupporting

confidence: 86%

Determination of Trimethylbismuth in the Human Body after Ingestion of Colloidal Bismuth Subcitrate

Boertz¹,

Hartmann²,

Sułkowski³

et al. 2008

Drug Metab Dispos

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“…The drug regimen should be based susceptibility testing using biopsies from the patient, stool specimens, or more commonly by knowledge of the success rates of different therapies in the local area and in one's practice. Other considerations include cost and availability of drugs and should take into account the difference in pharmacokinetics and pharmacodynamics of the drugs available [25][26][27][28][29] .…”

Section: Host Factors Influencing Treatment Successmentioning

confidence: 99%

New concepts of resistance in the treatment of Helicobacter pylori infections

Graham

Shiotani

2008

Nat Rev Gastroenterol Hepatol

316

368

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SummaryThe prevalence of antimicrobial resistance is now such that all patients should be considered as having resistant infections. Ideally therapy is based on pretreatment susceptibility testing. Empiric therapies should assume antimicrobial resistance and use higher doses for 14 days. Acceptable results are 90-94% cure intention to treat (Grade B) or greater. Clarithromycin-containing triple therapies now typically produce ≤80% cure ITT (Grade F) and are no longer acceptable empiric therapy. Current initial therapy options are between sequential therapy, concomitant therapy, and bismuth containing quadruple therapy. Sequential therapy has the potential to be improved to ≥95% cure ITT (Grade A) by continuing the amoxicillin through the second and/or by increasing the duration. Better appreciation of the role of acidity in phenotypic resistance has resulted in high cure rates with high dose PPI plus amoxicillin dual therapy; additional studies to devise better dual-based multidrug regimes are still needed. Antimicrobial choices following treatment failure is best approached by susceptibility testing. If not available, we recommended a bismuth containing quadruple therapy substituting a new drug for metronidazole/tinidazole and/or clarithromycin if they have been used previously. The alternate would be to use a 14 day high dose PPI, amoxicillin-based triple therapy with rifabutin, a fluoroquinolone, or furazolidone. KeywordsHelicobacter pylori; therapy; resistance; antibiotics; anti-secretory drugs; phenotypic drug resistance; cytochrome P450 "To read without reflecting is like eating without digesting". -86-462-1111-86-462- , FAX 81-86-464-1195 Review criteria: We searched the relevant papers by using computer-assisted bibliographic searches of PubMed through November 30, 2007 using combinations of the following terms: H. pylori combined with resistance, therapy, eradication, second, triple, quadruple, sequential, or rescue. We also reviewed the recent literature on pharmacokinetics and pharmacodynamics in relation to the drugs used in H. pylori therapy and the relation to host cytochrome P450 genotypes to treatment outcome. We did not perform meta-analyses. We reviewed only articles published in English.

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“…1). [9][10][11][12] Therefore, CYP2C19 contributes less to the overall metabolism of rabeprazole compared to lansoprazole, and is less in‰uenced by CYP2C19 genetic polymorphisms. 13) Genotypes of CYP2C19 are classied into three groups: homozygous extensive metabolizers (homEMs), heterozygous extensive metabolizers (hetEMs), and poor metabolizers (PMs).…”

Section: Introductionmentioning

confidence: 99%

Enantioselective Disposition of Lansoprazole and Rabeprazole in Human Plasma

Miura

2006

YAKUGAKU ZASSHI

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Lansoprazole is extensively metabolized by CYP2C19 and CYP3A4 in the liver, whereas rabeprazole is primarily converted non-enzymatically to rabeprazole-thioether, with only some being oxidized by CYP2C19 and CYP3A4. Lansoprazole and rabeprazole possess asymmetric sulfur in their chemical structure and have typically been used clinically as a racemic mixture. This article reviews the pharmacokinetic diŠerences between enantiomers of lansoprazole and rabeprazole in relation to the CYP2C19 genotypes. In our studies in healthy Japanese subjects, the magnitude of contribution of each lansoprazole enantiomer for CYP2C19 was greater than that for CYP3A4. CYP2C19 in‰uenced the disposition of (S )-lansoprazole to a greater extent than the ( R)-enantiomer. The R/S ratios for the AUC of lansoprazole in CYP2C19 homEMs, hetEMs and PMs was 12.7, 8.5 and 5.8, respectively. On the other hand, (R)-rabeprazole disposition was in‰uenced to a greater degree by CYP2C19 genetic polymorphisms than (S )-rabeprazole. However, the R/S ratios for the AUC of rabeprazole in CYP2C19 homEMs, hetEMs and PMs was only 1.8, 2.2 and 2.4, respectively, suggesting a lesser eŠect of CYP2C19 polymorphisms on the stereoselective disposition of rabeprazole compared to lansoprazole. Such a diŠerence in the AUC between rabeprazole enantiomers is likely to be dependent on stereoselectivity in the CYP3A4-mediated metabolic conversion from rabeprazole-thioether to rabeprazole. Both enantiomers of these PPIs have been reported to possess equal potency. Therefore, particularly with lansoprazole, the use of ( R)-lansoprazole alone would be highly desirable for use in clinical applications.

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Pharmacokinetic Considerations in the Eradication of Helicobacter Pylori

Cited by 103 publications

References 201 publications

Determination of Trimethylbismuth in the Human Body after Ingestion of Colloidal Bismuth Subcitrate

Determination of Trimethylbismuth in the Human Body after Ingestion of Colloidal Bismuth Subcitrate

New concepts of resistance in the treatment of Helicobacter pylori infections

Enantioselective Disposition of Lansoprazole and Rabeprazole in Human Plasma

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