Metered dose inhaler delivery of treprostinil for the treatment of pulmonary hypertension.
BACKGROUND
The stable prostanoid analogue treprostinil is approved as continuous infusion for treatment of pulmonary arterial hypertension. Unique drug characteristics may render this prostanoid feasible for inhalation therapy with a metered dose inhaler.


RESULTS
Randomised open label investigation of acute haemodynamic effects, safety and tolerability of inhaled treprostinil delivered in seconds by a metered dose inhaler (MDI-TRE). Inhaled nitric oxide (NO) and MDI-TRE were applied once during right heart catheter investigation to 39 consecutive patients with pre-capillary pulmonary hypertension. Doses of 30 microg, 45 microg and 60 microg MDI-TRE were investigated in separate groups of patients. Haemodynamics and blood gases were measured for 2h following treprostinil application. Acute haemodynamic responses to NO and MDI-TRE were comparable. MDI-TRE significantly improved haemodynamics compared to placebo inhalation. MDI-TRE induced effects were comparable to a historical control group that inhaled treprostinil from an ultrasonic nebuliser. The 120 min area under the curve for PVR changes due to placebo, 30 microg, 45 microg or 60 microg MDI-TRE was 1114+/-998, -870+/-940, -2450+/-2070 and -2000+/-900 min*%. Reduction of systemic vascular resistance and pressure were not clinically relevant. No significant side effects were observed. No impact on ventilation/perfusion matching by treprostinil was demonstrated in 5 patients with pre-existing gas exchange limitations by use of the multiple inert gas elimination technique.


CONCLUSIONS
The application of inhaled treprostinil with a metered dose inhaler is feasible and well tolerated. It induced a sustained pulmonary selective vasodilatation.
Voswinckel
Robert
R
University of Giessen Lung Center, Department of Internal Medicine, University Hospital Giessen, Klinikstrasse 36, 35392 Giessen, Germany. robert.voswinckel@uglc.de
Reichenberger
Frank
F
Gall
Henning
H
Schmehl
Thomas
T
Gessler
Tobias
T
Schermuly
Ralph Theo
RT
Grimminger
Friedrich
F
Rubin
Lewis J
LJ
Seeger
Werner
W
Ghofrani
Hossein A
HA
Olschewski
Horst
H
D000280:Administration, Inhalation; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D009569:Nitric Oxide / Q000008:administration & dosage; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; D009569:Nitric Oxide; D011464:Epoprostenol; C427248:treprostinil