派罗欣α2a和派罗欣2b的比较(11.1 AASLD)

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Comparison of Peginterferon Alfa-2a and Peginterferon-Alfa-2b Pharmacokinetics and Pharmacodynamic

Peginterferon-α2b/ Peg2b (Peg-Intron) and peginterferon-α2a/Peg2a (Pegasys), for the treatment of chronic hepatitis C virus (HCV) infection, differ in size (12 kDa and 40kDa, respectively) and site of polyethylene glycol moiety attachment. The in vivo consequences of these differences were investigated in a randomized, third-party blind, parallel-group trial.

Therapy-na飗e patients with chronic HCV infection genotype 1 (n=36) were randomized to receive Peg2b (1.5 μg/kg/wk) or Peg2a (180 μg/wk) monotherapy for 4 weeks, followed by peginterferon-α and ribavirin (13 mg/kg/day) combination therapy for 4 weeks.

Trial medication was prepared and administered by staff not otherwise involved in the trial. Intensive pharmacokinetic assays were performed throughout weeks 1 and 4.

Pharmacodynamic markers included viral load decline and interferon (IFN) response gene mRNA level.

Routine safety laboratory tests were carried out.

Results

While Peg2a concentration was 16 and 25 times greater than that of Peg2b at weeks 1 and 4, respectively, there was no difference in ex vivo antiviral assay AUC between the two agents.

Peg2b demonstrated a significantly greater viral load reduction in vivo during weeks 1 and 4 (Table below).

The safety evaluation revealed that absolute neutrophil count reductions from baseline were significantly lower in the Peg2b group than in the Peg2a group.

Antiviral Measure*

Peg2b

Peg2a

Week 1

Week 4

Week 1

Week 4

HCV RNA (log10.h/mL) AUC (0-168) Decline

Mean (SD)

212.7 (87.9)**

136.91 (82.36)**

110.9 (130.6)

19.61 (48.83)

Median

232.10

152.52

77.30

25.80

Max Log10 Reduction

Mean (SD)

2.17 (0.79)**

1.55 (0.86)**

1.17 (0.95)

0.46 (0.38)

Median

2.19

1.45

0.95

0.37

*Measured by TaqMan PCR with a sensitivity of 100 copies/mL **p=0.01

Conclusions

The authors conclude, 揟he pharmacological profile and biological response properties of Peg2b and Peg2a differ significantly. Further studies on the relationship between initial IFN response (as measured by acute viral load decline and IFN response gene up-regulation) and ultimate viral eradication are warranted.?/span>

11/01/04

Reference Marcelo Silva and others.COMPARISON OF PEGINTERFERON-α2A AND PEGINTERFERON-α2B PHARMACOKINETICS AND PHARMACODYNAMIC IN COMPARE, A RANDOMIZED, PROSPECTIVE, BLINDED TRIAL. Abstract 68 (poster). 55th AASLD. October 29-November 2, 2004. Boston, MA.