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Pulm Pharmacol Ther. 2008;21(3):516-21. doi: 10.1016/j.pupt.2007.11.006. Epub 2007 Dec 23.

Sildenafil for pulmonary hypertension: dose-dependent improvement in exercise performance.

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Department of Internal Medicine, University Hospital, Raemistrasse 100, CH-8091 Zurich, Switzerland.


Sildenafil has been widely used as an orphan drug for several years, mostly at a dose of 50mg tid. Since a recent randomized study showed no dose-response relationship, the target dose in future will be 20mg tid. This might, however, have a negative effect on patients being already on 50mg tid. During the past years we usually up-titrated the sildenafil dosage in monthly intervals from 12.5 to 25mg, and then finally to 50mg tid. Therefore, we wondered if a dose-response relationship could be found in a group of 23 patients, in whom we had measured a 6-min walking distance (6-MWD) at all time points. The 6-MWD was virtually unchanged during the treatment with sildenafil 12.5 and 25mg tid, respectively. However, there was a significant improvement by 34+/-63 and 26+/-47m in the 6-MWD after increasing the sildenafil dose to 50mg tid compared with baseline (p=0.015) and 25mg tid (p=0.014), respectively. In conclusion, these data suggest that sildenafil has a clinically relevant dose-response relationship with a significant improvement in 6-MWD only at a dose of 50mg tid.

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