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. 1989 May;27(5):581–586. doi: 10.1111/j.1365-2125.1989.tb03420.x

The contribution of nisoldipine-induced changes in liver blood flow to its pharmacokinetics after oral administration.

J van Harten 1, J Burggraaf 1, M Danhof 1, P van Brummelen 1, D D Breimer 1
PMCID: PMC1379923  PMID: 2757881

Abstract

1. The pharmacokinetics of nisoldipine (10 mg) was assessed in 10 healthy subjects after single dose and multiple dose oral administration. Apparent liver blood flow was measured, using ICG before and during the absorption phase of nisoldipine. 2. Apparent liver blood flow was increased both on acute and short-term administration of nisoldipine, basal flow being lower on multiple dosing than on acute administration (P less than 0.02). 3. A positive relationship was found between the increase in apparent liver blood flow during absorption of nisoldipine and the flow-dependent part of the total AUC of nisoldipine. 4. The findings of this study indicate that a variable liver blood flow response during the absorption phase of nisoldipine contributes to the pharmacokinetic variability of the drug, both on acute and multiple dose administration.

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Selected References

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  1. Bauer L. A., Stenwall M., Horn J. R., Davis R., Opheim K., Greene L. Changes in antipyrine and indocyanine green kinetics during nifedipine, verapamil, and diltiazem therapy. Clin Pharmacol Ther. 1986 Aug;40(2):239–242. doi: 10.1038/clpt.1986.169. [DOI] [PubMed] [Google Scholar]
  2. CAESAR J., SHALDON S., CHIANDUSSI L., GUEVARA L., SHERLOCK S. The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clin Sci. 1961 Aug;21:43–57. [PubMed] [Google Scholar]
  3. Feely J. Nifedipine increases and glyceryl trinitrate decreases apparent liver blood flow in normal subjects. Br J Clin Pharmacol. 1984 Jan;17(1):83–85. doi: 10.1111/j.1365-2125.1984.tb05003.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Guengerich F. P., Martin M. V., Beaune P. H., Kremers P., Wolff T., Waxman D. J. Characterization of rat and human liver microsomal cytochrome P-450 forms involved in nifedipine oxidation, a prototype for genetic polymorphism in oxidative drug metabolism. J Biol Chem. 1986 Apr 15;261(11):5051–5060. [PubMed] [Google Scholar]
  5. Kalow W. Genetic variation in the human hepatic cytochrome P-450 system. Eur J Clin Pharmacol. 1987;31(6):633–641. doi: 10.1007/BF00541288. [DOI] [PubMed] [Google Scholar]
  6. Kleinbloesem C. H., van Brummelen P., Faber H., Danhof M., Vermeulen N. P., Breimer D. D. Variability in nifedipine pharmacokinetics and dynamics: a new oxidation polymorphism in man. Biochem Pharmacol. 1984 Nov 15;33(22):3721–3724. doi: 10.1016/0006-2952(84)90165-5. [DOI] [PubMed] [Google Scholar]
  7. Lautt W. W., Greenway C. V. Conceptual review of the hepatic vascular bed. Hepatology. 1987 Sep-Oct;7(5):952–963. doi: 10.1002/hep.1840070527. [DOI] [PubMed] [Google Scholar]
  8. Lopez L. M., Rubin M. R., Holland J. P., Mehta J. L. Improvement in exercise performance with nisoldipine, a new second-generation calcium blocker, in stable angina patients. Am Heart J. 1985 Nov;110(5):991–996. doi: 10.1016/0002-8703(85)90198-x. [DOI] [PubMed] [Google Scholar]
  9. Meredith P. A., Pasanisi F., Elliott H. L., Reid J. L. The effect of nisoldipine on apparent liver blood flow and effective renal plasma flow. Br J Clin Pharmacol. 1985 Sep;20(3):235–237. doi: 10.1111/j.1365-2125.1985.tb05066.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Richardson P. D., Withrington P. G. Liver blood flow. II. Effects of drugs and hormones on liver blood flow. Gastroenterology. 1981 Aug;81(2):356–375. [PubMed] [Google Scholar]
  11. Swanson T. H., Green C. L. Nifedipine: more than a calcium channel blocker. Gen Pharmacol. 1986;17(3):255–260. doi: 10.1016/0306-3623(86)90038-8. [DOI] [PubMed] [Google Scholar]
  12. Van Harten J., Lodewijks M. T., Guyt-Scholten J. W., Van Brummelen P., Breimer D. D. Gas chromatographic determination of nisoldipine and one of its metabolites in plasma. J Chromatogr. 1987 Dec 25;423:327–333. doi: 10.1016/0378-4347(87)80359-6. [DOI] [PubMed] [Google Scholar]
  13. van Harten J., van Brummelen P., Lodewijks M. T., Danhof M., Breimer D. D. Pharmacokinetics and hemodynamic effects of nisoldipine and its interaction with cimetidine. Clin Pharmacol Ther. 1988 Mar;43(3):332–341. doi: 10.1038/clpt.1988.40. [DOI] [PubMed] [Google Scholar]
  14. van Harten J., van Brummelen P., Zeegers R. R., Danhof M., Breimer D. D. The influence of infusion rate on the pharmacokinetics and haemodynamic effects of nisoldipine in man. Br J Clin Pharmacol. 1988 Jun;25(6):709–717. doi: 10.1111/j.1365-2125.1988.tb05257.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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