VICTRELIS(boceprevir) capsule - America[美国药品]

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VICTRELIS(boceprevir) capsule(十八)

2013-10-12 22:42:30 来源: 作者: 【大中小】浏览:16800次评论:0条

irenone/ 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)

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 impairment had similar SCH534128 exposure as subjects with normal hepatic function. A similar magnitude of effect is anticipated for boceprevir. No dosage adjustment of VICTRELIS is recommended for patients with hepatic impairment [see Use in Specific Populations (8.7)]. See peginterferon alfa Package Insert for contraindication in patients with hepatic decompensation.

Renal Impairment

The pharmacokinetics of boceprevir was studied in non-HCV-infected subjects with end-stage renal disease (ESRD) requiring hemodialysis following a single 800 mg dose of VICTRELIS. The mean AUC of boceprevir was 10% lower in subjects with ESRD requiring hemodialysis relative to subjects with normal renal function. Hemodialysis removed less than 1% of the boceprevir dose. No dosage adjustment of VICTRELIS is required in patients with any degree of renal impairment.

Gender

Population pharmacokinetic analysis of VICTRELIS indicated that gender had no apparent effect on exposure.

Race

Population pharmacokinetic analysis of VICTRELIS indicated that race had no apparent effect on exposure.

Age

Population pharmacokinetic analysis of VICTRELIS showed that boceprevir exposure was not different across subjects 19 to 65 years old.