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British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1993 Nov;36(5):391–398. doi: 10.1111/j.1365-2125.1993.tb00386.x

Age-related differences in the pharmacokinetics and pharmacodynamics of lansoprazole.

Z Hussein 1, G R Granneman 1, D Mukherjee 1, E Samara 1, D L Hogan 1, M A Koss 1, J I Isenberg 1
PMCID: PMC1364610  PMID: 12959285

Abstract

1. The pharmacokinetics and pharmacodynamics of lansoprazole, an antisecretory and antiulcer agent, were evaluated in 12 older (> 60 years) and 12 younger (< 60 years) healthy men. 2. Doses of lansoprazole (15 or 30 mg) or placebo were each given once daily for 7 consecutive days in this randomized, double-blind, three-way crossover study. Plasma concentrations and urinary excretion of lansoprazole and its metabolites, and gastric acid secretion were monitored after dosing on days 1 and 7 of each treatment period. 3. Within each age group, lansoprazole pharmacokinetics were linear. The mean clearance and elimination half-life of lansoprazole were about 40% lower and higher, respectively, in the older subjects (CL0: 12-14 vs 20-24 1 h(-1); t1/2,z: 1.90-2.19 vs 1.26-1.44 h). 4. At each dose level, acid secretion was more inhibited in the older group. However, the AUC associated with a 50% decrease in acid secretion was similar (849 vs 892 ng ml(-1) h) for both age groups. Multiple dosing decreased the maximum possible inhibition more in the older group than in the younger group. 5. Since the decrease in acid output associated with equivalent AUCs on day 1 was similar for the two age groups, the greater difference between day 1 and day 7 secretion in the older group indicates that recovery of secretory activity may decline with increasing age.

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Selected References

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  1. Aoki I., Okumura M., Yashiki T. High-performance liquid chromatographic determination of lansoprazole and its metabolites in human serum and urine. J Chromatogr. 1991 Nov 15;571(1-2):283–290. doi: 10.1016/0378-4347(91)80457-n. [DOI] [PubMed] [Google Scholar]
  2. Ching M. S., Mihaly G. W., Angus P. W., Morgan D. J., Devenish-Meares S., Yeomans N. D., Smallwood R. A. Oral bioavailability of omeprazole before and after chronic therapy in patients with duodenal ulcer. Br J Clin Pharmacol. 1991 Feb;31(2):166–170. doi: 10.1111/j.1365-2125.1991.tb05506.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Greenblatt D. J., Sellers E. M., Shader R. I. Drug therapy: drug disposition in old age. N Engl J Med. 1982 May 6;306(18):1081–1088. doi: 10.1056/NEJM198205063061804. [DOI] [PubMed] [Google Scholar]
  4. Haruma K., Tokutomi T., Yoshihara M., Sumii K., Kajiyama G. Rapid growth of untreated esophageal squamous-cell carcinoma in 10 patients. J Clin Gastroenterol. 1991 Apr;13(2):129–134. doi: 10.1097/00004836-199104000-00003. [DOI] [PubMed] [Google Scholar]
  5. Hongo M., Ohara S., Hirasawa Y., Abe S., Asaki S., Toyota T. Effect of lansoprazole on intragastric pH. Comparison between morning and evening dosing. Dig Dis Sci. 1992 Jun;37(6):882–890. doi: 10.1007/BF01300386. [DOI] [PubMed] [Google Scholar]
  6. Hotz J., Kleinert R., Grymbowski T., Hennig U., Schwarz J. A. Lansoprazole versus famotidine: efficacy and tolerance in the acute management of duodenal ulceration. Aliment Pharmacol Ther. 1992 Feb;6(1):87–95. doi: 10.1111/j.1365-2036.1992.tb00548.x. [DOI] [PubMed] [Google Scholar]
  7. Jansen J. B., Lundborg P., Baak L. C., Greve J., Ohman M., Stöver C., Röhss K., Lamers C. B. Effect of single and repeated intravenous doses of omeprazole on pentagastrin stimulated gastric acid secretion and pharmacokinetics in man. Gut. 1988 Jan;29(1):75–80. doi: 10.1136/gut.29.1.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lind T., Cederberg C., Ekenved G., Haglund U., Olbe L. Effect of omeprazole--a gastric proton pump inhibitor--on pentagastrin stimulated acid secretion in man. Gut. 1983 Apr;24(4):270–276. doi: 10.1136/gut.24.4.270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lindberg P., Brändström A., Wallmark B., Mattsson H., Rikner L., Hoffmann K. J. Omeprazole: the first proton pump inhibitor. Med Res Rev. 1990 Jan-Mar;10(1):1–54. doi: 10.1002/med.2610100102. [DOI] [PubMed] [Google Scholar]
  10. Londong W., Barth H., Dammann H. G., Hengels K. J., Kleinert R., Müller P., Rohde H., Simon B. Dose-related healing of duodenal ulcer with the proton pump inhibitor lansoprazole. Aliment Pharmacol Ther. 1991 Jun;5(3):245–254. doi: 10.1111/j.1365-2036.1991.tb00025.x. [DOI] [PubMed] [Google Scholar]
  11. Müller P., Dammann H. G., Leucht U., Simon B. Human gastric acid secretion following repeated doses of AG-1749. Aliment Pharmacol Ther. 1989 Apr;3(2):193–198. doi: 10.1111/j.1365-2036.1989.tb00205.x. [DOI] [PubMed] [Google Scholar]
  12. Nagaya H., Inatomi N., Nohara A., Satoh H. Effects of the enantiomers of lansoprazole (AG-1749) on (H+ + K+)-ATPase activity in canine gastric microsomes and acid formation in isolated canine parietal cells. Biochem Pharmacol. 1991 Oct 24;42(10):1875–1878. doi: 10.1016/0006-2952(91)90584-r. [DOI] [PubMed] [Google Scholar]
  13. Nagaya H., Satoh H., Kubo K., Maki Y. Possible mechanism for the inhibition of gastric (H+ + K+)-adenosine triphosphatase by the proton pump inhibitor AG-1749. J Pharmacol Exp Ther. 1989 Feb;248(2):799–805. [PubMed] [Google Scholar]
  14. Nagaya H., Satoh H., Maki Y. Possible mechanism for the inhibition of acid formation by the proton pump inhibitor AG-1749 in isolated canine parietal cells. J Pharmacol Exp Ther. 1990 Mar;252(3):1289–1295. [PubMed] [Google Scholar]
  15. Regårdh C. G., Andersson T., Lagerström P. O., Lundborg P., Skånberg I. The pharmacokinetics of omeprazole in humans--a study of single intravenous and oral doses. Ther Drug Monit. 1990 Mar;12(2):163–172. doi: 10.1097/00007691-199003000-00010. [DOI] [PubMed] [Google Scholar]
  16. Regårdh C. G. Pharmacokinetics and metabolism of omeprazole in man. Scand J Gastroenterol Suppl. 1986;118:99–104. doi: 10.3109/00365528609090907. [DOI] [PubMed] [Google Scholar]
  17. Sanders S. W., Tolman K. G., Greski P. A., Jennings D. E., Hoyos P. A., Page J. G. The effects of lansoprazole, a new H+,K(+)-ATPase inhibitor, on gastric pH and serum gastrin. Aliment Pharmacol Ther. 1992 Jun;6(3):359–372. doi: 10.1111/j.1365-2036.1992.tb00057.x. [DOI] [PubMed] [Google Scholar]
  18. Satoh H., Inatomi N., Nagaya H., Inada I., Nohara A., Nakamura N., Maki Y. Antisecretory and antiulcer activities of a novel proton pump inhibitor AG-1749 in dogs and rats. J Pharmacol Exp Ther. 1989 Feb;248(2):806–815. [PubMed] [Google Scholar]
  19. Schmucker D. L. Aging and drug disposition: an update. Pharmacol Rev. 1985 Jun;37(2):133–148. [PubMed] [Google Scholar]
  20. Thomas F. J., Koss M. A., Hogan D. L., Isenberg J. I. Enprostil, a synthetic prostaglandin E2 analogue, inhibits meal-stimulated gastric acid secretion and gastrin release in patients with duodenal ulcer. Am J Med. 1986 Aug 18;81(2A):44–49. doi: 10.1016/s0002-9343(86)80010-9. [DOI] [PubMed] [Google Scholar]
  21. Triggs E. J., Hooper W. D., Dickinson R. G. The influence of age on drug metabolism. Implications for drug dosage. Med J Aust. 1984 Dec 8;141(12-13):823–827. [PubMed] [Google Scholar]
  22. Wallmark B., Lorentzon P., Larsson H. The mechanism of action of omeprazole--a survey of its inhibitory actions in vitro. Scand J Gastroenterol Suppl. 1985;108:37–51. [PubMed] [Google Scholar]

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