The pharmacokinetics and hemodynamics of sildenafil citrate in male hemodialysis patients

Eric B. Grossman, Suzanne K. Swan, Gary J. Muirhead, Michael Gaffney, Menger Chung, Herb DeRiesthal, Diane Chow, Leopoldo Raij

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background. Erectile dysfunction (ED) is highly prevalent in men with renal disease. The clearance of sildenafil citrate, a highly effective oral treatment for ED, is decreased in men with severe renal insufficiency, but the pharmacokinetic and hemodynamic profiles during maintenance hemodialysis in men with end-stage renal disease have not been studied. Methods. Fifteen men undergoing chronic outpatient maintenance hemodialysis received a single 50-mg oral dose of sildenafil on 2 occasions, once 2 hours before, and once 2 hours after hemodialysis, with randomized assignment to sequence. Blood and dialysate samples were collected, and hemodynamic measurements were made. Results. Hemodialysis did not significantly clear either sildenafil or its primary metabolite, UK-103,320. Administration after hemodialysis was associated with a 17% higher peak plasma concentration and earlier time to peak, which were not clinically meaningful, whereas the overall extent of absorption and the elimination half-life were not affected. The average extent of drug bound to plasma protein was approximately 96% in hemodialysis patients. Intradialytic hypotension was not observed more frequently when sildenafil was administered before hemodialysis. Systolic blood pressure tended to decrease less during hemodialysis when subjects were treated with sildenafil before dialysis. Conclusion. The present study demonstrates that sildenafil is not cleared by hemodialysis, and the pharmacokinetic profile resembles more closely that observed in normal volunteers than that observed in patients with severe renal insufficiency. In addition, we found that sildenafil does not promote intradialytic hypotension.

Original languageEnglish
Pages (from-to)367-374
Number of pages8
JournalKidney International
Volume66
Issue number1
DOIs
StatePublished - Jul 1 2004
Externally publishedYes

Fingerprint

Renal Dialysis
Pharmacokinetics
Hemodynamics
Erectile Dysfunction
Hypotension
Renal Insufficiency
Maintenance
Blood Pressure
Sildenafil Citrate
Dialysis Solutions
Chronic Kidney Failure
Half-Life
Blood Proteins
Dialysis
Healthy Volunteers
Outpatients
Kidney
Pharmaceutical Preparations

Keywords

  • Hemodialysis
  • Hemodynamics
  • Pharmacokinetics
  • Renal disease
  • Sildenafil citrate

ASJC Scopus subject areas

  • Nephrology

Cite this

Grossman, E. B., Swan, S. K., Muirhead, G. J., Gaffney, M., Chung, M., DeRiesthal, H., ... Raij, L. (2004). The pharmacokinetics and hemodynamics of sildenafil citrate in male hemodialysis patients. Kidney International, 66(1), 367-374. https://doi.org/10.1111/j.1523-1755.2004.00739.x

The pharmacokinetics and hemodynamics of sildenafil citrate in male hemodialysis patients. / Grossman, Eric B.; Swan, Suzanne K.; Muirhead, Gary J.; Gaffney, Michael; Chung, Menger; DeRiesthal, Herb; Chow, Diane; Raij, Leopoldo.

In: Kidney International, Vol. 66, No. 1, 01.07.2004, p. 367-374.

Research output: Contribution to journalArticle

Grossman, EB, Swan, SK, Muirhead, GJ, Gaffney, M, Chung, M, DeRiesthal, H, Chow, D & Raij, L 2004, 'The pharmacokinetics and hemodynamics of sildenafil citrate in male hemodialysis patients', Kidney International, vol. 66, no. 1, pp. 367-374. https://doi.org/10.1111/j.1523-1755.2004.00739.x
Grossman EB, Swan SK, Muirhead GJ, Gaffney M, Chung M, DeRiesthal H et al. The pharmacokinetics and hemodynamics of sildenafil citrate in male hemodialysis patients. Kidney International. 2004 Jul 1;66(1):367-374. https://doi.org/10.1111/j.1523-1755.2004.00739.x
Grossman, Eric B. ; Swan, Suzanne K. ; Muirhead, Gary J. ; Gaffney, Michael ; Chung, Menger ; DeRiesthal, Herb ; Chow, Diane ; Raij, Leopoldo. / The pharmacokinetics and hemodynamics of sildenafil citrate in male hemodialysis patients. In: Kidney International. 2004 ; Vol. 66, No. 1. pp. 367-374.
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abstract = "Background. Erectile dysfunction (ED) is highly prevalent in men with renal disease. The clearance of sildenafil citrate, a highly effective oral treatment for ED, is decreased in men with severe renal insufficiency, but the pharmacokinetic and hemodynamic profiles during maintenance hemodialysis in men with end-stage renal disease have not been studied. Methods. Fifteen men undergoing chronic outpatient maintenance hemodialysis received a single 50-mg oral dose of sildenafil on 2 occasions, once 2 hours before, and once 2 hours after hemodialysis, with randomized assignment to sequence. Blood and dialysate samples were collected, and hemodynamic measurements were made. Results. Hemodialysis did not significantly clear either sildenafil or its primary metabolite, UK-103,320. Administration after hemodialysis was associated with a 17{\%} higher peak plasma concentration and earlier time to peak, which were not clinically meaningful, whereas the overall extent of absorption and the elimination half-life were not affected. The average extent of drug bound to plasma protein was approximately 96{\%} in hemodialysis patients. Intradialytic hypotension was not observed more frequently when sildenafil was administered before hemodialysis. Systolic blood pressure tended to decrease less during hemodialysis when subjects were treated with sildenafil before dialysis. Conclusion. The present study demonstrates that sildenafil is not cleared by hemodialysis, and the pharmacokinetic profile resembles more closely that observed in normal volunteers than that observed in patients with severe renal insufficiency. In addition, we found that sildenafil does not promote intradialytic hypotension.",
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