Key result
Cinaciguat administration resulted in substantially higher drug exposure in moderate hepatic impairment compared to controls, while only minor increases were seen in mild hepatic impairment.
Why the study?
Does hepatic impairment affect the pharmacokinetics and pharmacodynamics of cinaciguat compared to healthy controls?
Observational (n=32)
Open-label
Does hepatic impairment affect the pharmacokinetics and pharmacodynamics of cinaciguat compared to healthy controls?
Cinaciguat dose adaptation may not be required in mild hepatic impairment, but moderate hepatic impairment leads to substantially higher drug exposure and vasodilatation.
May warrant PK caution with cinaciguat in moderate hepatic impairment; leaves open need for confirmatory dosing studies.
Cinaciguat is intended for use in patients with acute decompensated heart failure. The drug is eliminated predominantly via the liver and, therefore, the potential impact of hepatic impairment on cinaciguat pharmacokinetics needs to be determined. This nonrandomized, open-label, observational study investigated the pharmacokinetics of cinaciguat in individuals with mild (Child-Pugh A; n = 8) or moderate (Child-Pugh B; n = 8) hepatic impairment and matched healthy volunteers (n = 16). An exploratory analysis of pharmacodynamic parameters was also conducted. Individuals with mild hepatic impairment and their controls received a single (4-hour) intravenous infusion of 100 µg/h cinaciguat, whereas individuals with moderate hepatic impairment and their controls received 50 µg/h. Cinaciguat was well tolerated and had a favorable safety profile. The most frequent treatment-emergent adverse events were headache (4 participants) and spontaneous penile erection (2 participants). In individuals with mild hepatic impairment, only minor increases in plasma cinaciguat concentrations and no significant differences in pharmacodynamic parameters were observed, compared with controls. Individuals with moderate hepatic impairment had a substantially higher cinaciguat exposure than controls. This higher exposure was associated with more pronounced vasodilatation. This study demonstrates that in individuals with mild hepatic impairment, individual dose adaptation may not be required.
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Frey et al. (2011) conducted an observational in Hepatic impairment (n=32). Cinaciguat vs. Matched healthy volunteers was evaluated on Pharmacokinetics of cinaciguat (plasma concentrations). Cinaciguat administration resulted in substantially higher drug exposure in moderate hepatic impairment compared to controls, while only minor increases were seen in mild hepatic impairment.
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