Peginterferon α-2a (20 kDa) derived from Hansenula Polymorpha is a distinct variety of peginterferons (PEG-IFN). A pilot study of this drug was conducted on healthy human subjects to evaluate its safety and pharmacokinetic behavior in local population.
With due approval of the IEC operating under ICH-GCP guidelines; ten healthy male subjects were selected randomly from the Pakistani population after thorough screening and signing of the Informed consent for an open label, single dose study. Each subject received a subcutaneous injection of the drug (180 µg) in abdominal skin and blood samples were collected at 0 and 1, 2, 3, 6, 12, 24, 36, 60, 84, 108, 132 and 156 hours, and analyzed by a validated ELISA method for peginterferon α-2a (20kDa), Unipeg®.
The Mean ± SEM (standard error of mean) PK parameters were found to be: Cmax: 18.67±2.92 ng/ml (7.05-34.51); AUC0-∞: 1440±113 h.µg/l] (969-2101); Absorption Half-Life: 17.02±2.06 h (10.37-29.26), elimination half life: 41.437±6.21 h (18.51-78.97 h); volume of distribution 8.933±1.72 L (4.81-18.34), clearance: 112.6±8.21 ml/h (71.96–155.96).
The safety of the drug was evaluated by observation of adverse effects and evaluating the change in general health parameters, hematological and biochemical test results during and after the study.
No Sever Adverse Effect was observed however the most common adverse event (AE) was the fever; observed in all volunteers (n=10), headache (6), Fatigue (5), Vomiting (4) and diarrhea, loss of appetite, body ache was observed in 3 volunteers. Three out of ten volunteers demonstrated decrease in WBC and platelets count. Changes observed in hematology returned to normal values within 16 days.
The safety profile of UNIPEG® was found to be very similar to those of reported in literature for unmodified IFNs and other pegylated interferons generally used in therapy. Future clinical trials are recommended to further establish the safety profile and pharmacokinetics.
Infoplease. Viral hepatitis C: The silent killer. http://www.infoplease.com/cig/dangerous-diseases- epidemics/hepatitis-c-silent-killer.html [Accessed December, 2010
Ali SA, Donahue RM, Qureshi H, Vermund SH. Hepatitis B and hepatitis C in Pakistan: prevalence and risk factors. Int J Infect Dis 2009; 13; 9-19. Epub 2008 Oct 2.
Government of Pakistan. National program for prevention and control of hepatitis, government of Pakistan. http://www.pmpch.org, www.health.gov.pk. Accessed Feb, 2011.
World Health organization. Global alert and response; Hepatitis B. http://www.who.int/csr/disease/hepatitis/ whocdscsrlyo20022/en/index3.html [Accessed June, 2011
Pegasys Hoffmann-La Roche Inc., 340 Kingsland Street, Nutley, New Jersey, US. 2011
Bertram G. Katzung, Antiviral, Basic & clinical pharmacology. 10th Ed. United State of America. The McGraw-Hill Companies, Inc; 2007: 822-823.
K. Rajender Reddy, Marlene W. Modi, Simon Pedder. Use of peginterferon ?-2a (40 KD) (Pegasys®) for the treatment of hepatitis C. Adv Drug Deliv Rev 2002; 54; 571-586.
García-García et al. Pharmacokinetic and pharmacodynamic comparison of two “pegylated” interferon alpha-2 formulations in healthy male volunteers: a randomized, crossover, double-blind study. BMC Pharmacol 23 Nov, 2010, 10: 15. http://dx.doi.org/10.1186/1471-2210-10-15
Product Review: Chemistry, Manufacturing and Controls of Pegasys, VOLUMES/FOLDERS 2.1, 3.1, 4.1 THROUGH 4.15 by Nga Yen Nguyen, BLA 103964 issued by CBER Office of Therapeutics Research and Review, CBER Office of the Center Associate Director for Research
Bruce A. Luxon. Pegylated interferon for the treatment of chronic hepatitis C infection. Clin Ther 2002; 24; 1363-1383.
Zeuzem S, Feinman SV, Rasenack J, Heathcote EJ, Lai MY, Gane E, O'Grady J, Reichen J, Diago M, Lin A, Hoffman J, Brunda MJ. PEG IFN alfa-2a in patients with chronic hepatitis C. N Engl J Med 2000; 343: 1666-1672. http://dx.doi.org/10.1056/NEJM200012073432301
Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gonçales FL Jr, Häussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J. PEG IFN alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002; 347: 975-982. http://dx.doi.org/10.1056/NEJMoa020047
Esmat G, Fattah SA. Evaluation of a novel pegylated interferon alpha-2a (Reiferon RetardR) in Egyptian patients with chronic hepatitis C – genotype 4. Digestive and Liver Disease 2009; (Suppl 3): 17–19
Caliceti P. Pharmacokinetics of pegylated interferons: What is misleading? Digestive and Liver Disease 2004; 3 (suppl 36); 334-9. http://dx.doi.org/10.1016/S1590-8658(04)80002-1
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