The pharmacokinetics and hemodynamics of sildenafil citrate in male hemodialysis patients.
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.


CONCLUSIONS
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.
Grossman
Eric B
EB
Pfizer, Inc., New York, New York, USA. GrossE@Pfizer.com
Swan
Suzanne K
SK
Muirhead
Gary J
GJ
Gaffney
Michael
M
Chung
Menger
M
DeRiesthal
Herb
H
Chow
Diane
D
Raij
Leopoldo
L
D000328:Adult; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011687:Purines; D006435:Renal Dialysis; D000068677:Sildenafil Citrate; D013450:Sulfones
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate