7^th World Congress on Bioavailability & Bioequivalence: BA/BE Studies Summit August 29-31, 2016 Atlanta, Georgia, USA

Erum Dilshad has submitted her PhD thesis (Biochemistry/Molecular biology) at the age of 30 years from Quaid-i-Azam University Islamabad, Pakistan. She has published 4 papers in reputed journals. She has 5 years’ experience as lab technologist and researcher. She has been engaged in teaching the Molecular Biology techniques to class M.Sc. for two year at Department of Biochemistry Quaid-i-Azam University, Islamabad. She has worked at Shifa International Hospital Islamabad for 4 years (2010-2014) as principal technologist at immunohistochemistry section of laboratory. She used to perform different diagnostic tests of immunology and molecular biology (FISH, ELISA, direct/indirect immunofluorescence and routine immunohistochemistry tests along with Antinuclear antibody testing).

Despite of many advances in the treatment of malaria, it is still the fifth most prevalent disease worldwide and is one of the major causes of death in the developing countries which accounted for 584,000 deaths in 2013, as estimated by World Health Organization. Artemisinin from Artemisia annua is still one of the most effective treatments for malaria. Increasing the artemisinin content of A. annua plants by genetic engineering would improve the availability of this much-needed drug. \r\nIn this regard, a high artemisinin yielding hybrid of A. annua produced by the centre for novel agricultural products of the University of York, UK, was selected (artemisinin maximally 1.4%). As rol genes are potential candidates of biochemical engineering, genetic transformation of A. annua with Agrobacterium tumefaciens GV3101 harbouring vectors with rol B and rol C genes was carried out with the objective of enhancement of artemisinin content. Transgenic lines produced were analysed by the LC-MS for quantitative analysis of artemisinin and analogues. These high artemisinin yielding transgenics were also analysed by real time quantitative PCR to find the molecular dynamics of artemisinin enhancement. Genes of artemisinin biosynthetic pathway were studied including amorphadiene synthase (ADS), cytochrome P450, (CYP71AV1) and aldehyde dehydrogenase 1 (ALDH1). Trichome-specific fatty acyl-CoA reductase 1(TAFR1) is an enzyme involved in both trichome development and sesquiterpenoid biosynthesis and both processes are important for artemisinin biosynthesis. Thus, real time qPCR analysis of the TAFR1 gene was carried out, and trichome density was determined. Transgenics of rol B gene showed 2-9 fold increase in artemisinin, 4-12 fold increase in artesunate and 1.2-3 fold increase in dihydroartemisinin. Whereas in the case of rol C gene transformants, a 4 fold increase in artemisinin, 4-9 fold increase in artesunate and 1-2 fold increase in dihydroartemisinin concentration was observed. Transformants with the rol B gene had higher expression of these genes than rol C transformants. TAFR1 was also found to be more expressed in rol gene transgenics than wild type A. annua, which was also in accordance with the trichome density of the respective plant. Thus it was proved that rol B and rol C genes are effective in the enhancement of artemisinin content of A. annua, rol B gene being more active to play part in this enhancement than rol C gene.\r\n

Dr Muneesh Garg has completed his MD (Physician) from Dagestan State Medical Academy, Russia in the year 1997 and MD (Pharmacology) from Goverment Medical College, Patiala, Punjab, India in the year 2004. He has more than 17 years of experience in academia, clinical practice and clinical research. He is the principal investigator of Sitec Labs Pvt Ltd., Navi Mumbai, India, for more than 10 years and has completed more than 500 BA/BE studies. He has published many research papers in reputed journals.

Ipratropium Bromide is a short-acting anticholinergic bronchodilator used in the management of chronic obstructive pulmonary disease. The aim of these three studies was to determine the bioequivalence of test and reference formulations of Ipratropium Bromide HFA pMDI 20 μg/ actuation with and without charcoal blockade; and with spacer device. Study-1 was single dose, randomized, 4-period, 2‑sequence, laboratory-blinded, crossover, replicate design conducted in 90 healthy volunteers under fasting conditions with concurrent oral charcoal blockade. Study-2 was single dose, randomized, 2-period, 2‑sequence, laboratory-blinded, crossover design conducted in 24 healthy volunteers under fasting conditions without concurrent oral charcoal blockade. Study-3 was single dose, randomized, 2-period, 2‑sequence, laboratory-blinded, crossover design conducted in 64 healthy volunteers under fasting conditions with Aero Chamber Plus valved holding chamber. Blood samples were collected up to 24 hours post-dose for pharmacokinetic profiling. Safety evaluations included monitoring adverse events and vital signs as well as performing clinical laboratory tests. Plasma concentrations of Ipratropium were determined with a validated LC-MS/MS method. The 90% CI of Ipratropium were 91.30-99.91, and 90.42-97.77; 87.33- 121.30, and 88.94– 120.34; 87.21-99.83, and 91.66-97.94 for Cmax, and AUC0-t for study-1, study-2, and study-3 respectively. Since the 90% CI for Cmax and AUC0-t were within the 80 – 125% interval, it was concluded that test and reference formulations of Ipratropium Bromide HFA pMDI 20 µg per actuation are bioequivalent in their rate and extent of absorption with and without charcoal blockade; and with spacer device.

Alejandro Saúl Padrón has completed his PhD at the age of 33 years from Habana University. He is graduated from Russian University of Chemistry D. I. Mendeleiev. He is the General Director of the Center for Pharmaceuticals Research and Development, one of enterprises of BioCubaFarma Organization. He has published more than 25 papers in reputed journals and has been serving as director of a Bioequivalence Unit. He has provided training and support for the conduction of BE study in other countries.

The Cuban industry produces about of 70 % of pharmaceuticals (generic) included in the National List of Basic Drugs. The focus of this work is to share with pharmaceutical scientists, academic researchers, regulators and key opinion leaders,the Cuban experiences on bioavailability and Bioequivalence Studies of Pharmaceuticals.\r\nThrough a selected example (carbamazepine) we disclose the several stages of the studies, according to national and international regulations.\r\nCarbamazepine was discovered in 1953. It was first marketed in 1962.[7] It is available as a generic medication. It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.\r\nThe time-courses of plasma carbamazepine concentrations were followed in apparently healthy adult subjects who, at different times, took single oral drug dose of 200 mg. Volunteers received a single dose with 240 mL of water on each treatment days separated by a 2 week washout period. \r\nAfter dosing, serial blood samples were collected for a period of 190 h. plasma was analyzed for carbamazepine by a sensitive, reproducible and accurate HPLC method. Various pharmacokinetic parameters were calculated from plasma concentration of four (two Cuban, two imported) formulations. Correlation of dissolution test and pharmacokinetic parameters were discussed, as well as variability intra formulation, intra voluntaries and the sex influences on these parameters.\r\nBased on statistical inferences, it was concluded that carbamazepine formulations have similar tends in Cuban population.\r\n