European Journal of Clinical Pharmacology

, Volume 41, Issue 4, pp 351–354

Pharmacokinetics of paroxetine in patients with cirrhosis

  • K. Dalhoff
  • T. P. Almdal
  • K. Bjerrum
  • S. Keiding
  • H. Mengel
  • J. Lund
Originals

Summary

In a 14-day multiple-dose study the pharmacokinetics of paroxetine was investigated in 12 patients with alcoholic cirrhosis and in 6 subjects without liver disease. The dose of 20–30 mg paroxetine daily was adjusted to the reduction in liver function, as assessed by the galactose elimination capacity. Accordingly, all but two of the cirrhotic patients received 20 mg, while all six control subjects received 30 mg.

Dose-corrected, trough drug concentration at steady state (CSSmin) and dose-corrected AUC24h were significantly higher in the patients with liver diseases than in the control subjects [3.4 vs 1.5 ng · ml−1 per mg paroxetine and 89 vs 43 h (ng) · ml−1 per mg paroxetine]. The elimination t1/2 was prolonged [83 vs 36 h], but the difference was not statistically significant, and the cirrhotic patients were still able to clear almost all the paroxetine by metabolism. All but two patients with cirrhosis experienced nausea during the first two or three days after the first dose, while none of the controls had this symptom.

The study showed slower elimination of paroxetine and consequently higher plasma levels in patients with cirrhosis, suggesting that in the latter the dose of paroxetine should be in the lower end of the therapeutic range.

Key words

Paroxetine Cirrhosis pharmacokinetics multiple-dose study adverse effects 

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References

  1. 1.
    Kaye CM, Haddock RE, Langley PF et al. (1989) A review of the metabolism and pharmacokinetics of paroxetine in man. Acta Psychiatr Scand 80 [Suppl 350]: 60–75Google Scholar
  2. 2.
    Krastev Z, Terziivanov D, Vlahov V et al. (1989) The pharmacokinetics of paroxetine in patients with liver cirrhosis. Acta Psychiatr Scand 80 [Suppl 350]: 91–92Google Scholar
  3. 3.
    Døssing M, Poulsen HE, Andreasen PB, Tygstrup N (1982) A simple method for determination of antipyrine clearance. Clin Pharmacol Ther 32: 392–397Google Scholar
  4. 4.
    Tygstrup N (1966) Determination of the hepatic elimination capacity (Lm) of galactose by single dose injection. Scand J Clin Lab Invest 18 [Suppl 92]: 118–125Google Scholar
  5. 5.
    Tygstrup N (1977) Effect of sites for blood sampling in determination of the galactose elimination capacity. Scand J Clin Lab Invest 37: 333–338Google Scholar
  6. 6.
    Brett MA, Dierdorf HD, Zussman BD, Coates PE (1987) Determination of paroxetine in human plasma, using high-performance liquid chromatography with fluorescence detection. J Chromatogr 419: 438–444Google Scholar
  7. 7.
    Lundmark J, Thomsen IS, Fjord-Larsen T et al. (1989) Paroxetine: pharmacokinetic and antidepressant effect in the elderly. Acta Psychiatr Scand 80 [Suppl 350]: 76–80Google Scholar
  8. 8.
    Døssing M, Pilsgaard H, Rasmussen B, Poulsen HE (1983) Time course of phenobarbital and cimetidine mediated changes in hepatic drug metabolism. Eur J Clin Pharmacol 25: 215–222Google Scholar
  9. 9.
    Greb WH, Buscher G, Dierdorf HD, Köster FE, Wolf D, Mellows G (1989) The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine. Acta Psychiatr Scand 80 [Suppl 350]: 95–98Google Scholar
  10. 10.
    Bannister SJ, Houser VP, Hulse JD, Kisicki JC, Rasmussen JGC (1989) Evaluation of the potential for interactions of paroxetine with cimetidine, warfarin and digoxin. Acta Psychiatr Scand 80 [Suppl 350]: 102–106Google Scholar
  11. 11.
    Bass L, Keiding S (1988) Physiologically based models and strategic experiments in hepatic pharmacology. Biochem Pharmacol 37: 1425–1431Google Scholar
  12. 12.
    Sorrentino D, Potter BJ, Berk PD (1990) From albumin to the cytoplasm: the hepatic uptake of organic anions. In: Popper H, Schaffner F (eds) Progress in liver diseases. Saunders, PhiladelphiaGoogle Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • K. Dalhoff
    • 1
  • T. P. Almdal
    • 1
  • K. Bjerrum
    • 1
  • S. Keiding
    • 1
  • H. Mengel
    • 2
  • J. Lund
    • 2
  1. 1.Department of MedicineRigshospitaletCopenhagenDenmark
  2. 2.CNS DivisionNovo Nordisk A/SSøborgDenmark

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