Guideline on the Investigation of Bioequivalence CPMP/EWP/QWP/1401/98 Rev. 1. 20 January 2010. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/01/WC500070039.pdf. 5. Tothfalusi L, Endrenyi L, Hormones antagonist Arieta AG. Evaluation of bioequivalence for ZD1839 highly variable drugs with scaled average bioequivalence. Clin Pharmacokinet. 2009;48(11):725–43.PubMedCrossRef 6. European Medicines Agency. Committee for Medicinal Products for Human Use (CHMP) European public assessment report (EPAR) for ibandronic acid Sandoz. Issued: 17 February 2011. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002367/WC500109886.pdf.
7. European Medicines Agency. Committee for Medicinal Products for Human Use (CHMP) European public assessment report (EPAR) for ibandronic acid Teva. Issued: 17 September 2010 http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/001195/WC500097557.pdf.
8. Reginster PR-171 ic50 JY, Wilson KM, Dumont E, Bonvoisin B, Barrett J. Monthly oral ibandronate is well tolerated and efficacious in postmenopausal women: results from the monthly oral pilot study. J Clin Endocrinol Metab. 2005;90(9):5018–24.PubMedCrossRef”
“1 Introduction Head and neck squamous cell cancer accounts for 3 % of new cancer cases and 2 % of cancer mortality annually in the United States [1]. Globally, head and neck squamous cell carcinoma (HNSCC) affects over 500,000 patients each year, making it the sixth in incidence and the seventh in mortality in the world [2]. Current treatment options for most head and neck cancers continue to be surgical excision with or without radiation, radiation alone, or chemotherapy with radiation depending on location, stage of disease, and patient preference. While advances have been made in the delivery of treatment, little change
has been seen in the overall survival of head and neck cancer patients for decades [2]. Currently, no effective single agent chemotherapy treatment regimen is available for head and neck cancer. Additionally, oral chemotherapy is currently limited in its P-type ATPase use, usually as second- or third-line therapy or in a clinical trial. Fusaric acid (FA) is a novel compound from a novel class of nicotinic acid derivatives, which have activity against HNSCC. FA is produced by Fusarium species as a mycotoxin [3]. Mycotoxins are highly toxic compounds produced by fungi usually for the purposes of self-defense or to dissolve cell membranes as part of their fungal pathogenicity. Also known as 5-butlypicolinic acid, FA has been reported to have a number of pharmacologic effects in mammals including cardiovascular [4] and potential adverse neurological effects [5]. The therapeutic effects were observed at doses in the range of 10–30 mg/kg, while adverse effects were observed at a significantly higher dose of 100 mg/kg [5].