Search results for: Pharmacokinetics of Rolapitant in Patients With Mild to Moderate Hepatic Impairment.
#29329482 
2018/01/12
To Up
Pharmacokinetics of Rolapitant in Patients With Mild to Moderate Hepatic Impairment.
Rolapitant is a selective and long-acting neurokinin-1 receptor antagonist approved in an oral formulation in combination with other antiemetic agents for the prevention of delayed chemotherapy-induced nausea and vomiting in adults. This was a phase 1 open-label, parallel-group pharmacokinetic and safety study of a single oral dose of 180 mg of rolapitant and its major active metabolite, M19, in subjects with mild and moderate hepatic impairment compared with healthy matched controls. Pharmacokinetics were assessed by a mixed-model analysis of variance of log-transformed values for maximum observed plasma concentration (C ), observed time at C (t ), area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUC ), and AUC from time 0 to 120 hours (AUC ), with hepatic group as a fixed effect. Mean rolapitant C , AUC , and AUC were similar in the mild hepatic impairment and healthy control groups. In subjects with moderate hepatic impairment, AUC was similar and C was 25% lower than in healthy controls. Mean M19 C and AUC were similar in the mild hepatic impairment group and healthy controls, but <20% lower in those with moderate hepatic impairment versus healthy controls. Fraction of unbound rolapitant was comparable in all groups for rolapitant and M19. Rolapitant was well tolerated in all groups, without serious adverse events. Pharmacokinetic differences between healthy subjects and those with mild or moderate hepatic impairment are unlikely to pose a safety risk and do not warrant predefined dosage adjustment in the presence of hepatic impairment.Jing Wang, Xiaodong Wang, Zhi-Yi Zhang, Sujata Arora, Sharon Lu, Vikram Kansra
1399 related Products with: Pharmacokinetics of Rolapitant in Patients With Mild to Moderate Hepatic Impairment.
1 kit 1 G1mg500 gm.100 μg1 kit100 mg96 wells50100
Related Pathways
#28460548 //
To Up
Clinical pharmacology of neurokinin-1 receptor antagonists for the treatment of nausea and vomiting associated with chemotherapy.
Five NK-1 RA formulations are commercially available to treat the delayed phase of chemotherapy-induced nausea and vomiting (CINV) occurring between days 2-5 post chemotherapy (aprepitant oral capsule and suspension, fosaprepitant intravenous infusion, netupitant/palonosetron capsules and rolapitant tablet) but no direct comparative studies have been conducted to determine their relative clinical utility. Areas covered: Information on pharmacology and safety of the NK-1 RAs derived from PubMed showed that all bind the NK-1 receptor with high affinity and selectivity. There is substantial variation in the disposition and time course in the body of NK-1 RAs because of the differential effects of hepatic metabolism. Unlike netupitant and rolapitant, aprepitant is metabolized extensively by cytochrome P450 (CYP) 3A4. Aprepitant and netupitant also both inhibit CYP3A4. Consequently, aprepitant not only has a much shorter elimination half-life than netupitant and rolapitant but also a more prolific drug interaction profile. All of the NK-1 RAs are efficacious and safe, and are suitable for use in a range of different patient populations, including those with mild or moderate hepatic or renal impairment. Expert opinion: While discovery of NK-1 RAs represents a major breakthrough in CINV control, further work is needed to improve control of chemotherapy-induced nausea.Bernardo Rapoport, Teresa Smit