Enantioselective disposition of lansoprazole in extensive and poor metabolizers of CYP2C19

Kyoung Ah Kim, Ji Hong Shon, Ji-Young Park, Young Ran Yoon, Min Jung Kim, Doo Hee Yun, Moon Kyung Kim, In June Cha, Myung Ho Hyun, Jae Gook Shin

Research output: Contribution to journalArticle

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Abstract

Objective: To evaluate the enantioselective disposition of lansoprazole in relation to the genetic polymorphism of CYP2C19. Methods: A single oral dose of racemic lansoprazole (30 mg) was administered to 6 extensive metabolizers and 6 poor metabolizers whose genotypes were determined by use of polymerase chain reaction-restriction fragment length polymorphism. The pharmacokinetic parameters were estimated from the plasma concentrations of lansoprazole racemate, its enantiomers, and metabolites, which were measured for 24 hours after drug administration. The unbound fraction of lansoprazole enantiomers was determined by means of ultra-filtration of fresh human serum spiked with racemic lansoprazole. Results: The plasma concentrations of R(+)-lansoprazole were consistently higher than those of the S(-)-enantiomer in both extensive and poor metabolizers of CYP2C19, and the mean area under the plasma concentration-time curve of the (+)- and (-)-enantiomers showed 4.3- and 5.8-fold differences between poor and extensive metabolizers, respectively. The (+)/(-) ratios of lansoprazole clearance were not significantly different between poor and extensive metabolizers (0.19 ± 0.07 and 0.05 ± 0.08, respectively). The values for volume of distribution of the (-)-enantiomer were 3- and 10-fold greater, respectively, than those of the (+)-enantiomer in poor and extensive metabolizers, which was related to a 2-fold higher unbound fraction of the (-)-enantiomer. Conclusions: The effect of CYP2C19 genetic polymorphism on the enantioselective disposition of lansoprazole seems to be less significant than the effect on omeprazole and pantoprazole. The disposition of lansoprazole enantiomers appears to be influenced by enantioselective protein binding and by enantioselective metabolism of lansoprazole.

Original languageEnglish
Pages (from-to)90-99
Number of pages10
JournalClinical Pharmacology and Therapeutics
Volume72
Issue number1
DOIs
Publication statusPublished - 2002 Aug 12
Externally publishedYes

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Lansoprazole
Genetic Polymorphisms
Dexlansoprazole
Cytochrome P-450 CYP2C19
Omeprazole
Protein Binding
Restriction Fragment Length Polymorphisms
Pharmacokinetics
Genotype
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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Enantioselective disposition of lansoprazole in extensive and poor metabolizers of CYP2C19. / Kim, Kyoung Ah; Shon, Ji Hong; Park, Ji-Young; Yoon, Young Ran; Kim, Min Jung; Yun, Doo Hee; Kim, Moon Kyung; Cha, In June; Hyun, Myung Ho; Shin, Jae Gook.

In: Clinical Pharmacology and Therapeutics, Vol. 72, No. 1, 12.08.2002, p. 90-99.

Research output: Contribution to journalArticle

Kim, KA, Shon, JH, Park, J-Y, Yoon, YR, Kim, MJ, Yun, DH, Kim, MK, Cha, IJ, Hyun, MH & Shin, JG 2002, 'Enantioselective disposition of lansoprazole in extensive and poor metabolizers of CYP2C19', Clinical Pharmacology and Therapeutics, vol. 72, no. 1, pp. 90-99. https://doi.org/10.1067/mcp.2002.126176
Kim, Kyoung Ah ; Shon, Ji Hong ; Park, Ji-Young ; Yoon, Young Ran ; Kim, Min Jung ; Yun, Doo Hee ; Kim, Moon Kyung ; Cha, In June ; Hyun, Myung Ho ; Shin, Jae Gook. / Enantioselective disposition of lansoprazole in extensive and poor metabolizers of CYP2C19. In: Clinical Pharmacology and Therapeutics. 2002 ; Vol. 72, No. 1. pp. 90-99.
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abstract = "Objective: To evaluate the enantioselective disposition of lansoprazole in relation to the genetic polymorphism of CYP2C19. Methods: A single oral dose of racemic lansoprazole (30 mg) was administered to 6 extensive metabolizers and 6 poor metabolizers whose genotypes were determined by use of polymerase chain reaction-restriction fragment length polymorphism. The pharmacokinetic parameters were estimated from the plasma concentrations of lansoprazole racemate, its enantiomers, and metabolites, which were measured for 24 hours after drug administration. The unbound fraction of lansoprazole enantiomers was determined by means of ultra-filtration of fresh human serum spiked with racemic lansoprazole. Results: The plasma concentrations of R(+)-lansoprazole were consistently higher than those of the S(-)-enantiomer in both extensive and poor metabolizers of CYP2C19, and the mean area under the plasma concentration-time curve of the (+)- and (-)-enantiomers showed 4.3- and 5.8-fold differences between poor and extensive metabolizers, respectively. The (+)/(-) ratios of lansoprazole clearance were not significantly different between poor and extensive metabolizers (0.19 ± 0.07 and 0.05 ± 0.08, respectively). The values for volume of distribution of the (-)-enantiomer were 3- and 10-fold greater, respectively, than those of the (+)-enantiomer in poor and extensive metabolizers, which was related to a 2-fold higher unbound fraction of the (-)-enantiomer. Conclusions: The effect of CYP2C19 genetic polymorphism on the enantioselective disposition of lansoprazole seems to be less significant than the effect on omeprazole and pantoprazole. The disposition of lansoprazole enantiomers appears to be influenced by enantioselective protein binding and by enantioselective metabolism of lansoprazole.",
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T1 - Enantioselective disposition of lansoprazole in extensive and poor metabolizers of CYP2C19

AU - Kim, Kyoung Ah

AU - Shon, Ji Hong

AU - Park, Ji-Young

AU - Yoon, Young Ran

AU - Kim, Min Jung

AU - Yun, Doo Hee

AU - Kim, Moon Kyung

AU - Cha, In June

AU - Hyun, Myung Ho

AU - Shin, Jae Gook

PY - 2002/8/12

Y1 - 2002/8/12

N2 - Objective: To evaluate the enantioselective disposition of lansoprazole in relation to the genetic polymorphism of CYP2C19. Methods: A single oral dose of racemic lansoprazole (30 mg) was administered to 6 extensive metabolizers and 6 poor metabolizers whose genotypes were determined by use of polymerase chain reaction-restriction fragment length polymorphism. The pharmacokinetic parameters were estimated from the plasma concentrations of lansoprazole racemate, its enantiomers, and metabolites, which were measured for 24 hours after drug administration. The unbound fraction of lansoprazole enantiomers was determined by means of ultra-filtration of fresh human serum spiked with racemic lansoprazole. Results: The plasma concentrations of R(+)-lansoprazole were consistently higher than those of the S(-)-enantiomer in both extensive and poor metabolizers of CYP2C19, and the mean area under the plasma concentration-time curve of the (+)- and (-)-enantiomers showed 4.3- and 5.8-fold differences between poor and extensive metabolizers, respectively. The (+)/(-) ratios of lansoprazole clearance were not significantly different between poor and extensive metabolizers (0.19 ± 0.07 and 0.05 ± 0.08, respectively). The values for volume of distribution of the (-)-enantiomer were 3- and 10-fold greater, respectively, than those of the (+)-enantiomer in poor and extensive metabolizers, which was related to a 2-fold higher unbound fraction of the (-)-enantiomer. Conclusions: The effect of CYP2C19 genetic polymorphism on the enantioselective disposition of lansoprazole seems to be less significant than the effect on omeprazole and pantoprazole. The disposition of lansoprazole enantiomers appears to be influenced by enantioselective protein binding and by enantioselective metabolism of lansoprazole.

AB - Objective: To evaluate the enantioselective disposition of lansoprazole in relation to the genetic polymorphism of CYP2C19. Methods: A single oral dose of racemic lansoprazole (30 mg) was administered to 6 extensive metabolizers and 6 poor metabolizers whose genotypes were determined by use of polymerase chain reaction-restriction fragment length polymorphism. The pharmacokinetic parameters were estimated from the plasma concentrations of lansoprazole racemate, its enantiomers, and metabolites, which were measured for 24 hours after drug administration. The unbound fraction of lansoprazole enantiomers was determined by means of ultra-filtration of fresh human serum spiked with racemic lansoprazole. Results: The plasma concentrations of R(+)-lansoprazole were consistently higher than those of the S(-)-enantiomer in both extensive and poor metabolizers of CYP2C19, and the mean area under the plasma concentration-time curve of the (+)- and (-)-enantiomers showed 4.3- and 5.8-fold differences between poor and extensive metabolizers, respectively. The (+)/(-) ratios of lansoprazole clearance were not significantly different between poor and extensive metabolizers (0.19 ± 0.07 and 0.05 ± 0.08, respectively). The values for volume of distribution of the (-)-enantiomer were 3- and 10-fold greater, respectively, than those of the (+)-enantiomer in poor and extensive metabolizers, which was related to a 2-fold higher unbound fraction of the (-)-enantiomer. Conclusions: The effect of CYP2C19 genetic polymorphism on the enantioselective disposition of lansoprazole seems to be less significant than the effect on omeprazole and pantoprazole. The disposition of lansoprazole enantiomers appears to be influenced by enantioselective protein binding and by enantioselective metabolism of lansoprazole.

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