CYP2C19-guided design of a proton pump inhibitor dose regimen to avoid the need for pharmacogenetic individualisation in H. pylori eradication.
Objective: It has been demonstrated that genetic variation in CYP2C19 has a significant influence upon H. pylori eradication rates. We have determined a dosage regimen of lansoprazole that will provide EMs with exposure approximately equivalent to that obtained by PMs treated with standard doses and...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 67; no. 3; pp. 261 - 267 |
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| Autores principales: | , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Springer Nature
Mar2011
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104820855&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104820855 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Mar2011 vid: 67 iid: 3 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 104820855 58526459 10.1007/s00228-010-0928-9 NLM21079935 104820855 ppf: 261 ppct: 6 formats: fmt: @attributes: type: P tig: atl: CYP2C19-guided design of a proton pump inhibitor dose regimen to avoid the need for pharmacogenetic individualisation in H. pylori eradication. aug: au: Ward, Michael Foster, David affil: Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide Australia sug: subj: Lansoprazole Administration and Dosage Lansoprazole Pharmacokinetics Helicobacter Infections Drug Therapy Helicobacter Infections Familial and Genetic Lansoprazole Metabolism Confidence Intervals Descriptive Statistics Mann-Whitney U Test Human ab: Objective: It has been demonstrated that genetic variation in CYP2C19 has a significant influence upon H. pylori eradication rates. We have determined a dosage regimen of lansoprazole that will provide EMs with exposure approximately equivalent to that obtained by PMs treated with standard doses and determined the exposure that a PM would experience if they were to be treated with this 'EM optimised' lansoprazole dose. Methods: Non-compartmental pharmacokinetic parameters (AUC, C, t) for CYP2C19 genotypes were obtained from the literature. Primary pharmacokinetic parameters (CL, Vd, ka) for 200 virtual patients were calculated from the weighted non-compartmental variables and used to simulate a 7 day treatment course of twice daily lansoprazole, at standard and optimised doses for 1,000 patients. Results: The administration of 180 mg twice daily to CYP2C19 EMs results in approximately equivalent exposure to lansoprazole as the administration of standard 30 mg twice daily doses to PMs. Administration of this six-fold dose increase to EMs is predicted to result in only a 2.5-fold increase in C when compared with PMs receiving the standard 30 mg dose. Conclusion: We present a potential lansoprazole dosing regimen that should result in improved H. pylori eradication within CYP2C19 EMs and may not require individualisation. Whilst the optimised dose represents a significant increase, it is below that reported in the chronic management of Zollinger-Ellison syndrome. On the basis that treatment is of limited duration and lansoprazole is generally well tolerated, such an approach warrants further in vivo evaluation to confirm drug exposure, efficacy and tolerability. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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