ABSTRACT
The EU research initiative OrBiTo (oral biopharmaceutics tools) involving partners from academia, pharmaceutical industry, small medium enterprises and a regulatory agency was launched with the goal of improving tools to predict the absorption of drugs in humans and thereby accelerating the formulation development process. The OrBiTo project was divided into four work packages (WP), with WP2 focusing on characterization of drug formulations. The present work introduces the OrBiTo WP2 Decision Tree, which is designed to assist the investigator in choosing the most appropriate in vitro methods for optimizing the oral formulation design and development process. The WP2 Decision Tree consists of four stages to guide the investigator. At the first stage, the investigator is asked to choose the formulation type of interest. At the second stage, the investigator is asked to identify which type of equipment (compendial/modified/noncompendial) is preferred/available. At the third stage, characteristics of the active pharmaceutical ingredient (API) are evaluated and in the fourth stage of the decision tree, suitable experimental protocols are recommended. A link to the living Decision Tree document is provided, and we now invite the pharmaceutical sciences community to apply it to current research and development projects and offer suggestions for improvement and expansion.
Subject(s)
Biopharmaceutics/methods , Decision Trees , Pharmaceutical Preparations/administration & dosage , Administration, Oral , Drug Design , Drug Industry/methods , Drug Liberation , Humans , Pharmaceutical Preparations/metabolismABSTRACT
Several lines of evidence suggest an involvement of the noradrenergic neurotransmitter system in the pathogenesis of bipolar affective disorder (BPAD). Three genes for alpha-adrenergic receptors (ADRA) are located in chromosomal regions that showed evidence for linkage: The alpha(1c)-adrenergic (ADRA-1C) receptor gene on 8p21, the alpha(2a)-adrenergic (ADRA-2A) receptor gene on 10q25, and the alpha(2c)-adrenergic (ADRA-2C) receptor on 4p16. In a BPAD sample of 120 parent-offspring triads, we genotyped a 492 Cys/Arg variant in exon 2 of the ADRA-1C gene, a -1291 G/C variant in the 5'UTR of the ADRA-2A gene, and a STR marker (adra2c1) in the 5'UTR of the ADRA-2C gene. Using the Transmission Disequilibrium Test (TDT), no significant differences in transmissions were observed for any of the three ADRA genes.
Subject(s)
Bipolar Disorder/genetics , Chromosomes, Human, Pair 10/genetics , Chromosomes, Human, Pair 8/genetics , Genetic Variation/genetics , Receptors, Adrenergic, alpha-1/genetics , Receptors, Adrenergic, alpha-2/genetics , 5' Untranslated Regions/genetics , Child , Disease Transmission, Infectious , Family , Female , Gene Frequency , Genotype , Humans , Linkage Disequilibrium , MaleABSTRACT
A duplication of chromosome 15q24-q26 (DUP25) has been reported to be associated with anxiety disorders. We tested for the presence of DUP25 in a sample of 50 patients with panic disorder and 50 controls using a quantitative real-time PCR approach. Contrary to the original finding, our results were compatible with the absence of DUP25, and no significant difference could be detected between patients and controls ( P=1.0). Thus, our study does not support the hypothesis of an involvement of DUP25 in panic disorder.
