Drug Classification System Research Articles

Final Medicare Rule Doesn't Allay Patient-Care Concerns

Final Medicare Rule Doesn't Allay Patient-Care Concerns

Biopharmaceutic Classification System: A Scientific Framework for Pharmacokinetic Optimization in Drug Research

The tenets of biopharmaceutics, solubility and permeability, are of pivotal importance in new drug discovery and lead optimization due to the dependence of drug absorption and pharmacokinetics on these two properties. A classification system for drugs based on these two fundamental parameters, Biopharmaceutic Classification System (BCS), provides drug designer an opportunity to manipulate structure or physicochemical properties of lead candidates so as to achieve better "deliverability". Considering the facts for failure of NCEs, drug research, once concentrating on optimizing the efficacy and safety of the leads, dramatically transformed in the past two decades. With the enormous number of molecules being synthesized using combinatorial and parallel synthesis, high throughput methodologies for screening solubility and permeability has gained significant interest in pharmaceutical industry. Ultimate aim of the drug discovery scientist in pharmacokinetic optimization is to tailor the molecules so that they show the features of BCS class I without compromising on pharmacodynamics. Considerations to optimize drug delivery and pharmacokinetics right from the initial stages of drug design propelled need for "High Throughput Pharmaceutics" (HTP). In silico predictions and development of theoretical profiles for solubility and lipophilicity provides structure based biopharmaceutical optimization, while in vitro experimental models (microtitre plate assays and cell cultures) validate the predictions. Thus, biopharmaceutical characterization during drug design and early development helps in early withdrawal of molecules with insurmountable developmental problems associated with pharmacokinetic optimization.

Quantitative biopharmaceutics classification system: the central role of dose/solubility ratio.

To develop a quantitative biopharmaceutics drug classification system (QBCS) based on fundamental parameters controlling rate and extent of absorption. A simple absorption model that considers transit flow, dissolution, and permeation processes stochastically was used to illustrate the primary importance of dose/solubility ratio and permeability on drug absorption. Simple mean time considerations for dissolution, uptake, and transit were used to identify relationships between the extent of absorption and a drug's dissolution and permeability characteristics. The QBCS developed relies on a (permeability, dose/ solubility ratio) plane with cutoff points 2 x 10(-6)-10(-5) cm/s for the permeability and 0.5-1 (unitless) for the dose/solubility ratio axes. Permeability estimates, P(app) are derived from Caco-2 studies, and a constant intestinal volume content of 250 ml is used to express the dose/solubility ratio as a dimensionless quantity, q. A physiologic range of 250-500 ml was used to account for variability in the intestinal volume. Drugs are classified into the four quadrants of the plane around the cutoff points according to their P(app), q values, establishing four drug categories. i.e., I (P(app) > 10(-5) cm/s, q < or = 0.5), II (P(app) > 10(-5) cm/s, q > 1), III (P(app) < 2 x 10(-6) cm/s. q < or = 0.5), and IV (P(app) < 2 x 10(-6) cm/s, q > 1). A region for borderline drugs (2 x 10(-6) < P(app) < 10(-5) cm/s, 0.5 < q < 1) was defined too. For category I, complete absorption is anticipated, whereas categories II and III exhibit dose/ solubility ratio-limited and permeability-limited absorption, respectively. For category IV, both permeability and dose/solubility ratio are controlling drug absorption. Semiquantitative predictions of the extent of absorption were pointed out on the basis of mean time considerations for dissolution, uptake, and transit in conjunction with drug's dose/solubility ratio and permeability characteristics. A set of 42 drugs were classified into the four categories, and the predictions of intestinal drug absorption were in accord with the experimental observations. The QBCS provides a basis for compound classification into four explicitly defined drug categories using the fundamental biopharmaceutical properties, permeability, and dose/solubility ratio. Semiquantitative predictions for the extent of absorption are essentially based on these drug properties, which either determine or are strongly related to the in vivo kinetics of drug dissolution and intestinal wall permeation.

The Development of a Sustainable Drug Classification System for Humanitarian Disasters

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Biopharmaceutical characterization of oral immediate release drug products. In vitro/in vivo comparison of phenoxymethylpenicillin potassium, glimepiride and levofloxacin

The development of in vitro dissolution tests using the paddle and basket apparatus is described with respect to the qualification/validation of the testing procedure. Three examples of immediate release products containing phenoxymethylpenicillin potassium, glimepiride, and levofloxacin providing different solubility characteristics are evaluated. The solubility was high in the case of phenoxymethylpenicillin potassium and levofloxacin and low for glimepiride according to the biopharmaceutics classification system. The permeability is studied using the human colorectal carcinoma cell line CaCo-2. The permeability (10 −6cm/s) of phenoxymethylpenicillin potassium, glimepiride, and levofloxacin was high. The determined permeability data are confirmed by absorption data obtained by means of numerical deconvolution of plasma concentrations. Recommendations are given for the biopharmaceutical characterization of the three immediate release drug products, taking into account in vitro and in vivo comparison as well as the biopharmaceutics drug classification system. The evaluated acceptance criteria are the following: phenoxymethylpenicillin potassium (80% in 30 min), glimepiride (80% in 15 min) and levofloxacin (80% in 30 min). Typically, for immediate release formulations, one limit is specified for the dissolution to ensure the release of the active ingredient within the present time period. Since phenoxymethylpenicillin potassium and levofloxacin belong to Case 1, no in vitro/in vivo correlation is expected, absorption may be gastric emptying dependent. Glimepiride is categorized to Case 2. Nevertheless, a correlation with the in vivo dissolution profile does not exist, because of the pH-dependent low solubility of the drug. Finally, recommendations are made for the batch control of drug products in accordance with the four Cases.

Linear correlation of the fraction of oral dose absorbed of 64 drugs between humans and rats.

The preliminary work was presented at the meeting of the Expert Panel on Biopharmaceutics Drug Classification System of the Food and Drug Administration on October 21, 1997 at Food and Drug Administration in Rockville, Maryland. The content of this paper was also presented under the title, Drug absorption studies in vivo in rats for predicting fraction of drug absorbed in humans at the AAPS Workshop on Permeability Definitions and Regulatory Standards for Bioequivalance, August 17-19, 1998, Arlington. Virginia.

Human effective permeability data forrurosemide, hydrochlorthiazide, ketoprofen and naproxen to be used in the proposed biopharmaceutical drug classification system for IR-products

Human effective permeability data forrurosemide, hydrochlorthiazide, ketoprofen and naproxen to be used in the proposed biopharmaceutical drug classification system for IR-products

Drug classification system cost saving in Italy

Drug classification system cost saving in Italy

Electronic Surveillance of the Pharmacology-Toxicology Literature: The Need for Controlled Vocabularies and Registry Systems

Controlled vocabularies of "preferred names" and registry systems are essential in electronic indexing, storing, searching, and retrieving the world′s published literature. The most efficient and comprehensive search is accomplished by using the preferred name. Without a controlled vocabulary or a registry system, it would be necessary to remember every name that might have been used by authors since January 1966, in order to retrieve all the citations on a chemical from over 7.8 million citations currently in the National Library of Medicine′s MEDLINE and its backfiles. The task of creating the list of subject descriptors that make possible the surveillance of published literature via electronic databases requires the participation of the scientific community in developing domain-specific nomenclature, drug classification, controlled vocabularies, and registry systems as well. The biological unions of the International Council of Scientific Unions and its Committee on Data for Science and Technology are major contributors to the establishment and dissemination of standards for biological terminology and nomenclature. The objectives of the IUPHAR Nomenclature Committee include the development of a rational framework for the nomenclature of receptor classes or families and a classification for therapeutic agents. This will help define rules for the characterization and classification of receptors that are stable and easy to comprehend. The International Union of Pharmacology publishes guidelines for the classification of drugs and the nomenclature of receptors and ion channels.

Introduction and history of the use of electroencephalography in animal drug studies.

A brief review of the development and the state-of-the-art of EEG methods used to study drug effects is presented. Classification systems based on drug effects in animals kept awake artificially, and based on drug effects on the sleep-wake state duration and distribution are discussed. It is concluded that the techniques are there and the time is ripe to develop animal EEG-based drug classification systems with high predictive ability.

Effects of bepridil on cardiac electrophysiologic properties

The current classification system for antiarrhythmic drugs has several shortcomings; for example, electrophysiologic effects are defined in normal tissue, whereas antiarrhythmic drugs are often used clinically in diseased or injured tissue. Consideration of the electrophysiologic effects of bepridil in humans emphasizes the drawbacks of the classification system. Bepridil is primarily a calcium antagonist with class IV action. However, because the drug has class IA action as well, it should not be considered a typical class I or class IV agent. Bepridil has been observed to prolong the QT interval in the majority of patients in whom it is used for treatment of angina. However, in US clinical trials, including open extensions, only 7 cases of torsades de pointes have been recorded. In France, where the drug is approved for treatment of angina, the incidence of torsades de pointes was 0.01% in 1989. No consensus currently exists regarding what degree of QT prolongation constitutes increased risk for a ventricular proarrhythmic event. Based on current information, bepridil should be used cautiously in patients with a propensity toward hypokalemia, which can exacerbate or induce a proarrhythmic state. The drug should not be used in patients with a prolonged QT interval at baseline, a history of torsades de pointes, or long QT interval syndrome. Bepridil also should be avoided in patients with sinus node dysfunction or second- or third-degree atrioventricular block.

FDA drug classification system

The purpose and use of the FDA's classification system for new drug products are described. Investigational new drug applications (INDs) and new drug applications (NDAs) are submitted to the FDA's Center for Drug Evaluation and Research. To establish the priority of the product in the review process, expert reviewers classify each product according to chemical type and therapeutic potential. Drug products that receive a high therapeutic rating (e.g., 1AA or 1A) are reviewed for approval more quickly than drugs that receive a lower therapeutic rating (e.g., 1B or 1C). Because this system is the only national therapeutic rating system for drug products, it has been used in legislation, in clinical evaluation of new drug products as they are approved, and in formulary decisions. However, caution is needed because the therapeutic rating assigned at the time of the product's approval may not reflect its importance relative to all agents available at a later date. The FDA classification system was designed to guide new drug products through the application process and should be used only with caution for other purposes.

Drugs affecting blood rheology—a review

Many pharmacological substances act on blood cells, modifying their rheological properties. Studies performed on this subject have been quite varied and it is often difficult to draw conclusions from them.The author intends to propose a classification system for drugs according to their direct, indirect, global or specific effects on blood rheology.This classification is only preliminary since existing studies of the effect of drugs on blood rheology are fragmentary and often lack precision.

An objective classification of psychoactive drugs

1. 1. Among the many classifications of psychoactive drugs, the quantitative EEG system is both objective and useful. 2. 2. The measurement of EEG frequency, amplitude, variability, and pattern provides a basis to classify established psychoactive drugs, to assess new drugs, and to estimate their pharmacodynamics. 3. 3. The EEG system is based on a theory of association of EEG and behavior after psychoactive drugs; it is reliable and reproducible; and numerous laboratories carry out the analyses. 4. 4. The relative independence of EEG systems from intuition makes it the most objective psycho-active drug classification system available.