Treatment of secondary pulmonary hypertension with bosentan and its pharmacokinetic monitoring in ESRD.
Pulmonary hypertension (PH) is a rare disease with a very poor prognosis. Certain pharmacologic approaches, which reduce pulmonary arterial pressure (PAP) and thereby prevent end-stage cardiopulmonary failure, have been used during recent years. Endothelin-1 has been found to be involved in the pathogenesis of PH. The dual endothelin-receptor antagonist, bosentan, was recently approved for the treatment of pulmonary arterial hypertension. The drug is mainly cleared by hepatic elimination. Severe renal dysfunction does not affect the single-dose pharmacokinetics of bosentan to a clinically relevant extent. Whether renal replacement therapy, however, interferes with the pharmacokinetics of bosentan is unknown. The authors report on the use of bosentan (125 mg twice daily) and its pharmacokinetic monitoring in a 19-year-old woman with PH and end-stage renal disease secondary to scleroderma. Treatment was well tolerated without drug-specific adverse effects. After 12 months of treatment, pulmonary arterial pressure had normalized (48 mm Hg before start of treatment, 27 mm Hg at last follow-up). On the basis of analyzing samples from Genius-hemodialysis by a liquid chromatography assay with tandem mass spectrometry detection, the authors determined the bosentan dialysis clearance to be as low as 3.5 mL/min. Bosentan for the treatment of secondary PH seems to be safe as well as effective in end-stage renal disease patients and no adjustment of the bosentan dosing regimen appears necessary.
Liefeldt
Lutz
L
Division of Nephrology Department of Pathology, Center for Cardiovascular Research (CCR), Charité, Humboldt-University, Berlin, Germany.
van Giersbergen
Paul L M
PL
Dingemanse
Jasper
J
Rudolph
Birgit
B
Walde
Torsten
T
Budde
Klemens
K
Neumayer
Hans-H
HH
Hocher
Berthold
B
D000328:Adult; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077300:Bosentan; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000150:complications; D012595:Scleroderma, Systemic / Q000150:complications*; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D013449:Sulfonamides; D000077300:Bosentan