Interactions of sildenafil and tacrolimus in men with erectile dysfunction after kidney transplantation.
OBJECTIVE
To study the pharmacokinetics of the combined use of sildenafil (which may provide an effective treatment for patients with erectile dysfunction after kidney transplantation) and tacrolimus, as interactions between them are expected because of a common elimination pathway.


METHODS
Ten male patients (age 29 to 52 years) were included. Because of its importance in transplant recipients, medication remained unchanged. On day 1, tacrolimus was administered routinely, and blood samples for tacrolimus assays were drawn at predefined times. On day 2, sildenafil was added and blood was collected for assays of tacrolimus, sildenafil, and the sildenafil metabolite UK103,320 (UK) at the indicated times. Blood pressure was monitored on both study days. Sildenafil and UK were assessed by high-pressure liquid chromatography and tacrolimus was assessed by microparticle enzyme immunoassay.


RESULTS
No effects of sildenafil on the tacrolimus pharmacokinetics were found. However, in the patients studied, the sildenafil and UK pharmacokinetics were altered compared with the results of previous studies. The mean peak concentration of sildenafil was higher by 44% and the area under the concentration-time data increased by 90%. The elimination half-life was prolonged (4.7 hours compared with 3 hours in healthy volunteers). The area under the concentration-time data for UK was about threefold larger than in healthy volunteers, and the half-life was prolonged from 3.8 hours to 11.4 hours. Pronounced blood pressure drops were observed.


CONCLUSIONS
Tacrolimus or the concomitant medication or the disease itself might have altered the sildenafil and UK pharmacokinetics. Because of the drop in blood pressure, sildenafil therapy should start at the lowest dose and any antihypertensive medication should be adjusted.
Christ
B
B
Department of Internal Medicine, University of Giessen, Giessen, Germany.
Brockmeier
D
D
Hauck
E W
EW
Friemann
S
S
D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology*; D006207:Half-Life; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D016559:Tacrolimus / Q000493:pharmacokinetics / Q000494:pharmacology*
D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D016559:Tacrolimus