Bosentan

AUCtau was the area under the curve calculated to the end of the dosing interval, tau. The effect of co-administration of imatinib at two doses (200 and 400 mg) on the pharmacokinetics of bosentan was performed on dose normalized AUCtau of bosentan. A mixed effects linear model was fitted to the log-transformed PK parameters. This model included treatment (i.e., dose of imatinib) as a fixed effect, and participant as a random effect. Estimates for the treatment differences and associated 90% confidence intervals were obtained from the above model. These estimates and confidence intervals were then "back-transformed" to the original scale, giving, for each dose level of imatinib, the ratio of imatinib + co-administered sildenafil and bosentan (test) relative to the co-administered drugs alone (sildenafil + bosentan) (reference).

AUCtau was the area under the curve calculated to the end of the dosing interval, tau. The effect of co-administration of imatinib at two doses (200 and 400 mg) on the pharmacokinetics of sildenafil was performed on dose normalized AUCtau of sildenafil. A mixed effects linear model was fitted to the log-transformed PK parameters. This model included treatment (i.e., dose of imatinib) as a fixed effect, and participant as a random effect. Estimates for the treatment differences and associated 90% confidence intervals were obtained from the above model. These estimates and confidence intervals were then "back-transformed" to the original scale, giving, for each dose level of imatinib, the ratio of imatinib + co-administered sildenafil and bosentan (test) relative to the co-administered drugs alone (sildenafil + bosentan) (reference).

Cmax was the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after dose administration. The effect of co-administration of imatinib at two doses (200 and 400 mg) on the pharmacokinetics of bosentan was performed on dose normalized Cmax of bosentan. A mixed effects linear model was fitted to the log-transformed PK parameters. This model included treatment (i.e., dose of imatinib) as a fixed effect, and participant as a random effect. Estimates for the treatment differences and associated 90% confidence intervals were obtained from the above model. These estimates and confidence intervals were then "back-transformed" to the original scale, giving, for each dose level of imatinib, the ratio of imatinib + co-administered sildenafil and bosentan (test) relative to the co-administered drugs alone (sildenafil + bosentan) (reference).

Cmax was the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after dose administration. The effect of co-administration of imatinib at two doses (200 and 400 mg) on the pharmacokinetics of sildenafil was performed on dose normalized Cmax of sildenafil. A mixed effects linear model was fitted to the log-transformed PK parameters. This model included treatment (i.e., dose of imatinib) as a fixed effect, and participant as a random effect. Estimates for the treatment differences and associated 90% confidence intervals were obtained from the above model. These estimates and confidence intervals was then "back-transformed" to the original scale, giving, for each dose level of imatinib, the ratio of imatinib + co-administered sildenafil and bosentan (test) relative to the co-administered drugs alone (sildenafil + bosentan) (reference).