Interferon evaluation

Weiner, N., Williams, N., Birch, G., Ramachandran, R., Shipman, C., Jr., and Flynn, G. (1989),Topical delivery of liposomally encapsulated interferon evaluated in a cutaneous herpes guinea pig model, Antimicrob. Agents Chemoter., 33,1217-1221. 

Center for Biologies Evaluation and Research (CBER). This center is responsible for the regulation and approval of ah biological products intended for use in the treatment, prevention, or cure of diseases or injuries to humans. A biological product is any vims, therapeutic semm, toxin, antitoxin, vaccine, blood or blood component or derivative, or analogous product (5). It also includes products produced by biotechnology, such as interferons and erythropoietins. 

As medical researchers continue to explore the therapeutic properties of interferons, chemical engineers will continue to provide the expertise needed to make available the quantities of these molecules necessary for clinical evaluation. 

Bain VG, Kaita KD, Yoshida EM, Swain MG, Heathcote EJ, Neumann AU, FisceUa M, Yu R, Osborn BE, Cronin PW, Ereimuth WW, McHutchison JG, Subramanian GM (2006) A phase 2 study to evaluate the antiviral activity, safety, and pharmacokinetics of recombinant human albumin-interferon alfa fusion protein in genotype 1 chronic hepatitis C patients. J Hepatol 44 671-678... 

Balan V Nelson DR, Sulkowski MS, Everson GT, Lambiase LR, Wiesner RH, Dickson RC, Post AB, Redfleld RR, Davis GL, Neumann AU, Osborn BE, Ereimuth WW, Subramanian GM (2006) A Phase I/II study evaluating escalating doses of recombinant human albumin-interferon-alpha fusion protein in chronic hepatitis C patients who have failed previous interferon-alpha-based therapy, Antivir Ther 11 35 5... 

In addition, stndies evaluating interferon alpha/beta and interlenkin-16 expression have shown snbstantial antiviral effects against HlV-1 in vitro and in a humanized mouse model (Cremer et al. 2000 Lanret et al. 1994 Sanhadji et al. 1997 Zhou etal. 1997). 

Lactide/glycoUde polymers have been investigated for delivery of several other macromolecules. Synthetic double-stranded RNA, poly-isosinic acid/polycytidylic acid, a potent inducer of interferon, was formulated in a 53 47 copolymer of DL-lactide-co-glycoUde. The microspheres were evaluated in mice challenged with Right Valley fever virus. More than 16 days protection was afforded versus only 3 days for controls (137). 

Persons with confirmed chronic hepatitis B should be evaluated for treatment, which may include interferon, pegylated interferon, lamivudine, adefovir dipivoxil, or entecavir. The drug of choice for chronic hepatitis B depends on the patient s past medical history, aminotransferase level, HBV DNA level, and most importantly, HBeAg status. 

Individuals with confirmed chronic hepatitis C should be evaluated for treatment with pegylated interferon with or without ribavirin. 

While there are no FDA-approved treatments for hepatitis D, interferon has been shown to be effective.46 48 Various doses have been evaluated, with the most effective treatment being 9 million units three times weekly.47 Seventy-one percent of patients who were treated with this regimen for 48 weeks had normalized ALT levels.47 Adverse effects and monitoring parameters for interferon therapy are similar to treatment for hepatitis C. In some situations, patients infected with hepatitis D who develop hepatic decompensation and ESLD may need to undergo liver transplantation. 

Interferon-a causes hypothyroidism in up to 39% of patients being treated for hepatitis C infection. Patients may develop a transient thyroiditis with hyperthyroidism prior to becoming hypothyroid. The hypothyroidism may be transient as well. Asians and patients with preexisting anti-TPOAbs are more likely to develop interferon-induced hypothyroidism. The mechanism of interferon-induced hypothyroidism is not known. If LT4 replacement is initiated, it should be stopped after 6 months to re-evaluate the need for replacement therapy. 

Younes, H. and Amsden, B. 2002. Interferon-gamma therapy evaluation of routes of administration and delivery systems. Journal of Pharmaceutical Sciences 91(1), 2-17. 

The in vivo antitumor effects of interferons are believed to be related to both augmentation of natural killer cell activity and antiproliferative effects. Antiproliferative activity probably also accounts for the bone marrow suppression observed in some individuals given IFN and could potentially produce effects in a routine preclinical reproduction or teratology evaluation. Dosing studies performed in... 

This approach appears somewhat irrational and without much scientific merit, since many of these new molecules are minimally toxic or nontoxic by this sort of acute evaluation. As in the case of interferons or monoclonal antibodies, the toxic effects observed in humans might not be predicted from safety assessments in rodents. An appropriate test species should be selected. Is the rat or mouse the appropriate species to evaluate a species-specific rDNA protein such as human growth hormone or interferons, or would nonhuman primates be more suitable Does the nonhuman primate really offer any advantages There is some consensus that the nonhuman primate may be a more appropriate species for testing some rDNA human proteins. 

Alpha interferons, including peginterferon alfa-2b, cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Closely monitor patients with periodic clinical and laboratory evaluations. Withdraw from therapy patients with persistently severe or worsening signs or symptoms of... 

Chronic progressive MS The safety and efficacy of interferon beta in chronic progressive MS have not been evaluated. 

Karau, C., Pongpaibul, Y, and Schmidt, PC., Quantitative evaluation of human leukocyte interferon-entrapped in liposomes, Drug Delivery, 3, 59-62, 1996. 

Intracavitary administration of various agents has been used for patients with malignant pleural or peritoneal effusions. Intraperitoneal instillations of cisplatin, etoposide, bleomycin, 5-fluorouracil, and interferon are well tolerated and are being evaluated in patients with ovarian carcinomas, in whom the tumor is frequently restricted to the peritoneal cavity. 

Arlen, P.A., Falconer, R., Cherukumilli, S., Cole, A., Cole, A.M., Oishi, K.K., and Daniell, H. (2007). Field production and functional evaluation of chloroplast-derived interferon-alpha2b. Plant Biotechnol. J. 5(4) 511-525. 

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