title: Sildenafil for pulmonary hypertension: dose-dependent improvement in exercise performance.
abstract: 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.
authors.affiliation: Department of Internal Medicine, University Hospital, Raemistrasse 100, CH-8091 Zurich, Switzerland.
authors.forename: Riina Marjaana
authors.initials: RM
authors.lastname: Spring
authors.forename: Silvia
authors.initials: S
authors.lastname: Ulrich
authors.forename: Lars C
authors.initials: LC
authors.lastname: Huber
authors.forename: Rudolf
authors.initials: R
authors.lastname: Speich
authors.forename: Marco
authors.initials: M
authors.lastname: Maggiorini
authors.forename: Ursula
authors.initials: U
authors.lastname: Treder
authors.forename: Manuel
authors.initials: M
authors.lastname: Fischler
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D000077300:Bosentan; D004305:Dose-Response Relationship, Drug; D015444:Exercise / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology* / Q000523:psychology; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D011687:Purines / Q000627:therapeutic use; D011788:Quality of Life; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000627:therapeutic use; D013450:Sulfones / Q000627:therapeutic use*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*; D016138:Walking / Q000502:physiology
chemical_list: D000959:Antihypertensive Agents; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013449:Sulfonamides; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D000077300:Bosentan