Tension Pulmonary hypertension is a progressive disease and only rarely results in chronic obstruction of small pulmonary arteries, leading to failure of the right ventricle, and conclude Lich lead GSK1838705A to death. PAHs in the context of HIV is associated with a particularly poor prognosis, and diagnosis and treatment are unerl Ugly. PAH therapies include antagonists of endothelin, prostacyclin analogs and inhibitors of phosphodiesterase type 5 Prostacyclin analogs are not known, substrates, inhibitors or inducers of CYP450 system, and relevant pharmacokinetic interactions with antiretrovirals are unlikely. A summary of the known and m Resembled interactions between PAHs and ARV treatment is included in Table 2. Bosentan, a mixed antagonist of endothelin receptors with an affinity t to endothelin A and B was demonstrated efficacy in HIV-associated PAH.
Bosentan is a substrate of CYP2C9 and CYP3A4, and is an inducer of CYP2C9 and CYP3A4. In a study PCI-24781 of three-way intersection, in tw Lf healthy male pattern subjects, the participants re U 125 mg bosentan twice t Possible and lopinavir / ritonavir 400/100 mg twice t Was like, alone or in combination to 9.5 days. In the presence of bosentan AUC of lopinavir and ritonavir were 14% and 17%, respectively, which was not reduced as clinically significant. In contrast, exposure to bosentan was significantly increased Ht. In the first 4 days after co-administration, increases ht bosentan concentrations up to 48 times, and at steady state was the ratio Ratio of geometric mean AUC 5.22 and 6.12 for Cmax was.
The increased Hte exposure was obtained with a Hten side effects associated with bosentan, associated mainly headache and vomiting. No subjects had a Erh Increase in liver enzymes. Therefore be performed, bosentan, is when boosted PIs reached steady state to avoid the maximum effect of inhibiting the metabolism of bosentan. In patients with chronic PI treatment, bosentan at a lower dose of 62.5 mg once t Possible or every other day to start. Patients who need ongoing therapy with bosentan He Verst opening a PI regimen RKT, bosentan should be discontinued for at least 36 hours before the start of the boosted PI and then again 10 days after the start of PI 62.5 mg once t resembled or every other day. Response to bosentan therapy through improvements in capacity, the severity of the NYHA status and hours Thermodynamic measurements are investigated by right heart catheter.
Parameter monitoring toxicity t of bosentan include headache, flushing, gastrointestinal effects, An Chemistry, signs and symptoms of liver damage Ending, worsening of heart failure and lung That. Although lopinavir and ritonavir concentrations not significantly reduced by bosentan in the previous study, k nnte The complete enzyme induction by bosentan is not reached, and excluded a further decrease in the levels of PI k Can. Adequate monitoring of antiretroviral efficacy and CT is recommended, especially when using boosted PI regimens involving lower doses of ritonavir. Bosentan with unboosted atazanavir resistance is specified, the plasma concentrations of atazanavir may be reduced. A case report of VER Published already mentioned HNT an m Possible interaction between bosentan and unboosted indinavir results in reduced plasma concentration of indinavir.
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