The effects of cimetidine and antacid on the pharmacokinetic profile of sildenafil citrate in healthy male volunteers.
OBJECTIVE
To examine the effect of concomitant cimetidine or antacid administration on the pharmacokinetic profile of sildenafil citrate in healthy male volunteers in two open-label, randomized studies.


METHODS
The first study was a parallel-group design in which 22 healthy male volunteers received sildenafil (50 mg) on days 1 and 5 and cimetidine (800 mg) or placebo on days 3, 4, 5, and 6. Blood samples were collected predose and at specified times up to 48 h postdose on days 1 and 5 to determine plasma levels of sildenafil and its metabolite, UK-103,320. The second study was a two-way crossover design in which 12 volunteers received sildenafil with or without a 30-ml dose of a magnesium hydroxide/aluminium hydroxide antacid. Blood samples were collected and analysed as in the first study. The two study periods were separated by at least 14 days.


RESULTS
Coadministration of cimetidine had no statistically significant effect on the tmax or kel of sildenafil but caused a statistically significant increase in sildenafil AUCt and Cmax of 56% and 54%, respectively (P<0.01). Differences between the two treatment groups were smaller for the metabolite than for sildenafil, although cimetidine treatment did significantly (P<0.05) increase the AUCt for UK-103,320 by 30%. Antacid coadministration had no statistically significant effect on any pharmacokinetic parameter of sildenafil or UK-103,320. Whether taken alone, with cimetidine, or with an antacid, sildenafil was well tolerated. Most adverse events were mild in nature, and no subject withdrew from either study for any reason related to the drug.


CONCLUSIONS
Cimetidine co-administration produced an increase in sildenafil plasma levels; however, this increase is not sufficient to warrant dosage adjustment of either drug. Antacid coadministration had no effect on the pharmacokinetic profile of sildenafil.
Wilner
Keith
K
Pfizer Global Research and Development, San Diego, CA, USA and Anapharm Inc, Sainte-Foy, Quebec, Canada.
Laboy
Lucia
L
LeBel
Marc
M
D000328:Adult; D000536:Aluminum Hydroxide / Q000008:administration & dosage / Q000494:pharmacology; D000863:Antacids / Q000008:administration & dosage / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D002927:Cimetidine / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D004338:Drug Combinations; D006207:Half-Life; D006801:Humans; D008276:Magnesium Hydroxide / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D010879:Piperazines / Q000009:adverse effects / Q000493:pharmacokinetics*; D011687:Purines; D011744:Pyrimidinones / Q000493:pharmacokinetics; D000068677:Sildenafil Citrate; D013450:Sulfones
D000863:Antacids; D000897:Anti-Ulcer Agents; D004338:Drug Combinations; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D011744:Pyrimidinones; D013450:Sulfones; C109995:UK 103320; D000536:Aluminum Hydroxide; D002927:Cimetidine; D000068677:Sildenafil Citrate; D008276:Magnesium Hydroxide