Dose-response evaluation of the antisecretory effect of continuous infusion intravenous lansoprazole regimens over 48 h

Colin Howden, D. C. Metz, B. Hunt, M. Vakily, M. Kukulka, F. Amer, N. Samra

Research output: Contribution to journalArticle

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Abstract

Background: Attainment of intragastric pH < 6.0 may require high-dose continuously infused proton pump therapy. Aim: To assess the pharmacokinetic and pharmacodynamic dose-responses of continuous infusion regimens of lansoprazole. Methods: Healthy adult subjects were assigned to lansoprazole 60-mg intravenous bolus, followed by 6-mg/h continuous infusion; a 90-mg intravenous bolus followed by 6-, 7.5-, or 9-mg/h continuous infusion; or placebo. Results: Mean intragastric pH values for lansoprazole regimens ranged from 4.8 to 5.2 (0-24 h), 5.5 to 6.0 (>24 to 48 h) and 5.2 to 5.6 (0-48 h). Within these three intervals, the percentages of time intragastric pH exceeded 4, 5 and 6 ranged from 65% to 96%, 54% to 88% and 30% to 61% respectively. Pharmacokinetic parameters were dose-independent with steady-state plasma concentrations achieved within 6-12 h postdose and maintained over 48 h. The mean systemic clearance of lansoprazole was lower in CYP2C19 heterozygous metabolizers than in homozygous extensive metabolizers (9.2 vs. 16.5 L/h), with substantial variability resulting in overlapping ranges of clearance values for both subpopulations. All lansoprazole regimens were well-tolerated. Conclusions: Lansoprazole administered as a 60-mg intravenous bolus followed by 6-mg/h continuous infusion produced intragastric pH effects comparable with those of higher dosage regimens.

Original languageEnglish (US)
Pages (from-to)975-984
Number of pages10
JournalAlimentary Pharmacology and Therapeutics
Volume23
Issue number7
DOIs
StatePublished - Apr 1 2006

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Lansoprazole
Intravenous Infusions
Pharmacokinetics

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology
  • Pharmacology (medical)

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Dose-response evaluation of the antisecretory effect of continuous infusion intravenous lansoprazole regimens over 48 h. / Howden, Colin; Metz, D. C.; Hunt, B.; Vakily, M.; Kukulka, M.; Amer, F.; Samra, N.

In: Alimentary Pharmacology and Therapeutics, Vol. 23, No. 7, 01.04.2006, p. 975-984.

Research output: Contribution to journalArticle

Howden, Colin ; Metz, D. C. ; Hunt, B. ; Vakily, M. ; Kukulka, M. ; Amer, F. ; Samra, N. / Dose-response evaluation of the antisecretory effect of continuous infusion intravenous lansoprazole regimens over 48 h. In: Alimentary Pharmacology and Therapeutics. 2006 ; Vol. 23, No. 7. pp. 975-984.
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abstract = "Background: Attainment of intragastric pH < 6.0 may require high-dose continuously infused proton pump therapy. Aim: To assess the pharmacokinetic and pharmacodynamic dose-responses of continuous infusion regimens of lansoprazole. Methods: Healthy adult subjects were assigned to lansoprazole 60-mg intravenous bolus, followed by 6-mg/h continuous infusion; a 90-mg intravenous bolus followed by 6-, 7.5-, or 9-mg/h continuous infusion; or placebo. Results: Mean intragastric pH values for lansoprazole regimens ranged from 4.8 to 5.2 (0-24 h), 5.5 to 6.0 (>24 to 48 h) and 5.2 to 5.6 (0-48 h). Within these three intervals, the percentages of time intragastric pH exceeded 4, 5 and 6 ranged from 65{\%} to 96{\%}, 54{\%} to 88{\%} and 30{\%} to 61{\%} respectively. Pharmacokinetic parameters were dose-independent with steady-state plasma concentrations achieved within 6-12 h postdose and maintained over 48 h. The mean systemic clearance of lansoprazole was lower in CYP2C19 heterozygous metabolizers than in homozygous extensive metabolizers (9.2 vs. 16.5 L/h), with substantial variability resulting in overlapping ranges of clearance values for both subpopulations. All lansoprazole regimens were well-tolerated. Conclusions: Lansoprazole administered as a 60-mg intravenous bolus followed by 6-mg/h continuous infusion produced intragastric pH effects comparable with those of higher dosage regimens.",
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N2 - Background: Attainment of intragastric pH < 6.0 may require high-dose continuously infused proton pump therapy. Aim: To assess the pharmacokinetic and pharmacodynamic dose-responses of continuous infusion regimens of lansoprazole. Methods: Healthy adult subjects were assigned to lansoprazole 60-mg intravenous bolus, followed by 6-mg/h continuous infusion; a 90-mg intravenous bolus followed by 6-, 7.5-, or 9-mg/h continuous infusion; or placebo. Results: Mean intragastric pH values for lansoprazole regimens ranged from 4.8 to 5.2 (0-24 h), 5.5 to 6.0 (>24 to 48 h) and 5.2 to 5.6 (0-48 h). Within these three intervals, the percentages of time intragastric pH exceeded 4, 5 and 6 ranged from 65% to 96%, 54% to 88% and 30% to 61% respectively. Pharmacokinetic parameters were dose-independent with steady-state plasma concentrations achieved within 6-12 h postdose and maintained over 48 h. The mean systemic clearance of lansoprazole was lower in CYP2C19 heterozygous metabolizers than in homozygous extensive metabolizers (9.2 vs. 16.5 L/h), with substantial variability resulting in overlapping ranges of clearance values for both subpopulations. All lansoprazole regimens were well-tolerated. Conclusions: Lansoprazole administered as a 60-mg intravenous bolus followed by 6-mg/h continuous infusion produced intragastric pH effects comparable with those of higher dosage regimens.

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