Transgenic avian-derived recombinant human interferon-alpha2b (AVI-005) in healthy subjects: an open-label, single-dose, controlled study.
نویسندگان
چکیده
BACKGROUND/AIMS This study characterized the safety and pharmacological properties of AVI-005, a novel glycosylated recombinant human interferon-alpha2b produced from the egg whites of chickens transfected with human cDNA. METHODS 18 healthy volunteers received single subcutaneous rising doses (0.5, 1.66 or 5 million international units, MIU) of AVI-005. A randomized parallel comparator group of 10 subjects received 5 MIU of unglycosylated IFN-alpha2b (Intron A). The pharmacokinetic parameters t1/2, tmax, Cmax, AUC0-24h, Vd, and clearance were compared between AVI-005 and unglycosylated IFN-alpa2b. RESULTS At equipotent doses, AVI-005 had a larger AUC0-24h than the control interferon. Pharmacodynamic markers ofneopterin and beta2-microglobulin for the two treatments were similar. These markers were increased by AVI-005 in a dose-dependent manner. Pharmacodynamic responses to treatment with AVI-005 were shown by the change in mRNA expression for interferon inducible protein kinase and 2'5'-oligoadenylate synthetase. Adverse events in the two groups were qualitatively and quantitatively similar. CONCLUSION AVI-005 demonstrates biological activity and pharmaco-kinetic properties in humans that support further development.
منابع مشابه
Pharmacokinetics and Bioavailability Comparison of two oral Tablet Formulations of Escitalopram 20 mg: A Single-Dose, Open-Label, Two-Period Crossover Study in Healthy Indian Adult Subjects
This study was done to assess bioequivalence between test and reference formulations of escitalopram oxalate 20 mg in healthy Indian male subjects. This single-dose, randomized, open-label, 2-period crossover study was carried out in 12 Healthy Indian Male volunteers aged 18 to 55 years under fasting conditions with a wash out of 14 days. The subjects were randomly assigned to receive the test...
متن کاملA glycosylated recombinant human granulocyte colony stimulating factor produced in a novel protein production system (AVI-014) in healthy subjects: a first-in human, single dose, controlled study
BACKGROUND AVI-014 is an egg white-derived, recombinant, human granulocyte colony-stimulating factor (G-CSF). This healthy volunteer study is the first human investigation of AVI-014. METHODS 24 male and female subjects received a single subcutaneous injection of AVI-014 at 4 or 8 mcg/kg. 16 control subjects received 4 or 8 mcg/kg of filgrastim (Neupogen, Amgen) in a partially blinded, parall...
متن کاملStudy on the Effect of Solution Conditions on Heat Induced-Aggregation of Human Alpha Interferon
A major problem in the formulation of therapeutic proteins is the irreversible protein aggregation. Recombinant human interferon alpha2b (rhIFN2b) has poor stability and undergoes physical degradation. The aim of this study was to investigate the effect of solution conditions on the heat-induced aggregation of rhIFNα2b. The protein was incubated for 1 h at 40°C–70°C and for up to 240 h at 50C...
متن کاملStudy on the Effect of Solution Conditions on Heat Induced-Aggregation of Human Alpha Interferon
A major problem in the formulation of therapeutic proteins is the irreversible protein aggregation. Recombinant human interferon alpha2b (rhIFN2b) has poor stability and undergoes physical degradation. The aim of this study was to investigate the effect of solution conditions on the heat-induced aggregation of rhIFNα2b. The protein was incubated for 1 h at 40°C–70°C and for up to 240 h at 50C...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- International journal of clinical pharmacology and therapeutics
دوره 45 3 شماره
صفحات -
تاریخ انتشار 2007