ly × 7 days 800 mg three times daily × 12 days 0.86
(0.56–1.32) 0.96
(0.79–1.17) 1.31
(1.04–1.65)
Ritonavir 100 mg daily × 12 days 400 mg three times daily × 15 days 0.73
(0.57–0.93) 0.81
(0.73–0.91) 1.04
(0.62–1.75)
Efavirenz 600 mg daily × 16 days 800 mg three times daily × 6 days 0.92
(0.78–1.08) 0.81
(0.75–0.89) 0.56
(0.42–0.74)
Tenofovir 300 mg daily × 7 days 800 mg three times daily × 7 days 1.05
(0.98–1.12) 1.08
(1.02–1.14) 1.08
(0.97–1.20)
Peginterferon alfa-2b 1.5 mcg/kg subcutaneous weekly × 2 weeks 400 mg three times daily × 1 week 0.88
(0.66–1.18) 1.00*
(0.89–1.13) N/A
*No effect = 1.00
Table 7 Summary of the Effect of Boceprevir on Co-administered Drugs in Healthy Subjects or HCV Positive Genotype-1 Subjects Co-administered Drug Co-administered Drug Dose/Schedule Boceprevir Dose/Schedule Ratio Estimate of Co-administered Pharmacokinetic Parameters (in Combination vs. Alone)
(90% CI of the Ratio Estimate) *
Change in mean Cmax Change in mean AUC(τ)
N/A = not available
Midazolam 4 mg single oral dose 800 mg three times daily × 6 days 2.77
(2.36–3.25) 5.30
(4.66–6.03)
Efavirenz 600 mg daily × 16 days 800 mg three times daily × 6 days 1.11
(1.02–1.20) 1.20
(1.15–1.26)
Drospirenone/ Ethinyl estradiol Drospirenone:
3 mg + Ethinyl estradiol :
0.02 mg daily × 14 days 800 mg three times daily × 7 days Drospirenone: 1.57
(1.46–1.70)
Ethinyl estradiol: 1.00
(0.91–1.10) Drospirenone: 1.99
(1.87–2.11)
Ethinyl estradiol: 0.76
(0.73–0.79)
Tenofovir
300 mg daily × 7 days 800 mg three times daily × 7 days 1.32
(1.19–1.45) 1.05
(1.01–1.09)
Peginterferon alfa-2b 1.5 mcg/kg subcutaneous weekly × 2 weeks 200 mg or 400 mg three times daily × 1 week N/A 0.99† , ‡
(0.83–1.17)
*No effect = 1.00
†0–168 hours
‡Reported AUC is 200 mg and 400 mg cohorts combined.
Elimination
Boceprevir is eliminated with a mean plasma half-life (t½) of approximately 3.4 hours. Boceprevir has a mean total body clearance (CL/F) of approximately 161 L/hr. Following a single 800 mg oral dose of 14C-boceprevir, approximately 79% and 9% of the dose was excreted in feces and urine, respectively, with approximately 8% and 3% of the dosed radiocarbon eliminated as boceprevir in feces and urine. The data indicate that boceprevir is eliminated primarily by the liver.
Special Populations
Hepatic Impairment
The pharmacokinetics of boceprevir was studied in adult non-HCV infected subjects with normal, mild (Child-Pugh score 5–6), moderate (Child-Pugh score 7–9), and severe (Child-Pugh score 10–12) hepatic impairment following a single 400 mg dose of VICTRELIS. The mean AUC of the active diastereomer of boceprevir (SCH534128) was 32% and 45% higher in subjects with moderate and severe hepatic impairment, respectively, relative to subjects with normal hepatic function. Mean Cmax values for SCH534128 were 28% and 62% higher in moderate and severe hepatic impairment, respectively. Subjects with mild hepatic impair |
