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The Journal of Pharmacology and... Jul 2012The isobole is well established and commonly used in the quantitative study of agonist drug combinations. This article reviews the isobole, its derivation from the... (Review)
Review
The isobole is well established and commonly used in the quantitative study of agonist drug combinations. This article reviews the isobole, its derivation from the concept of dose equivalence, and its usefulness in providing the predicted effect of an agonist drug combination, a topic not discussed in pharmacology textbooks. This review addresses that topic and also shows that an alternate method, called "Bliss independence," is inconsistent with the isobolar approach and also has a less clear conceptual basis. In its simplest application the isobole is the familiar linear plot in cartesian coordinates with intercepts representing the individual drug potencies. It is also shown that the isobole can be nonlinear, a fact recognized by its founder (Loewe) but neglected or rejected by virtually all other users. Whether its shape is linear or nonlinear the isobole is equally useful in detecting synergism and antagonism for drug combinations, and its theoretical basis leads to calculations of the expected effect of a drug combination. Numerous applications of isoboles in preclinical testing have shown that synergism or antagonism is not only a property of the two agonist drugs; the dose ratio is also important, a fact of potential importance to the design and testing of drug combinations in clinical trials.
Topics: Animals; Dose-Response Relationship, Drug; Drug Combinations; Drug Interactions; Drug Synergism; Humans; Pharmaceutical Preparations; Pharmacology
PubMed: 22511201
DOI: 10.1124/jpet.112.193474 -
Journal of Natural Medicines Sep 2021Traditional herbal medicines, which have been used in the matured traditional medical systems as well as those have been used in ethnic medical systems, are invaluable... (Review)
Review
Traditional herbal medicines, which have been used in the matured traditional medical systems as well as those have been used in ethnic medical systems, are invaluable resources of drug seeds. Ethnobotanical and ethnopharmacological survey may provide useful information of these herbal medicines, which are valuable for searching new bioactive molecules. From this viewpoint, we have been performing the ethnobotanical and ethnopharmacological field studies in Yunnan Province and Guangxi Zhuang Autonomous Region, China, and Mongolia. Phytochemical studies on traditional herbal medicines were performed based on the information obtained by our ethnobotanical survey. Herbal medicines used in Uzbekistan and Bangladesh were also investigated on the basis of the ethnopharmacological information obtained from collaborative researchers in the respective regions. Some studies were carried out for searching active substance(s) based on bioassay-guided fractionation and isolation. Over 150 new molecules were isolated in these studies, and their various biological activities were also demonstrated. This review summarizes the results of phytochemical studies of those traditional herbal medicines as well as biological activities of the isolated molecules.
Topics: China; Ethnobotany; Ethnopharmacology; Phytochemicals; Phytotherapy; Plants, Medicinal
PubMed: 34255289
DOI: 10.1007/s11418-021-01545-7 -
Anesthesiology Apr 2010
Topics: Analgesics, Opioid; Chemistry, Pharmaceutical; Guidelines as Topic; Mental Disorders; Pain; Patient Care Management; Risk Assessment; Substance-Related Disorders; United States; United States Food and Drug Administration
PubMed: 20216398
DOI: 10.1097/ALN.0b013e3181cdefb4 -
Acta Pharmaceutica (Zagreb, Croatia) Dec 2013Many modern drugs are poorly water soluble substances, which causes difficulties in the development of solid dosage forms with sufficient bioavailability. Preparation of... (Review)
Review
Many modern drugs are poorly water soluble substances, which causes difficulties in the development of solid dosage forms with sufficient bioavailability. Preparation of liquisolid systems (LSS) is a novel technique for improving solubility, dissolution and bioavailability of such drugs. The basic principle of LSS preparation is conversion of the drug in liquid state into a free-flowing, compressible, dry powder through its absorption into suitable excipients - porous carriers (aluminometasilicates, microcrystalline cellulose), subsequently coated with material having high absorption capacity (silicon dioxide commonly known as colloidal silica). LSS exhibit advantages such as lower production costs compared to soft capsules, simple processing and enhanced drug release. The main benefit is higher bioavailability of the liquid drug, caused by a large surface area available for absorption. The article tries to clarify specific aspects connected with the formulation of LSS: properties of excipients (surface area, absorption capacity), variables related to the processing (solubility, liquid load factor) and dosage form evaluation.
Topics: Biological Availability; Chemistry, Pharmaceutical; Drug Carriers; Drug Compounding; Excipients; Humans; Pharmaceutical Preparations; Porosity; Powders; Solubility
PubMed: 24451071
DOI: 10.2478/acph-2013-0034 -
AAPS PharmSciTech 2008The physical-chemical properties of interest for controlled release (CR) dosage form development presented are based on the author's experience. Part I addresses... (Review)
Review
The physical-chemical properties of interest for controlled release (CR) dosage form development presented are based on the author's experience. Part I addresses selection of the final form based on a logical progression of physical-chemical properties evaluation of candidate forms and elimination of forms with undesirable properties from further evaluation in order to simplify final form selection. Several candidate forms which could include salt, free base or acid, polymorphic and amorphic forms of a new chemical entity (NCE) or existing drug substance (DS) are prepared and evaluated for critical properties in a scheme relevant to manufacturing processes, predictive of problems, requiring small amounts of test materials and simple analytical tools. A stability indicating assay is not needed to initiate the evaluation. This process is applicable to CR and immediate release (IR) dosage form development. The critical properties evaluated are melting, crystallinity, solubilities in water, 0.1 N HCl, and SIF, hygrodymamics, i.e., moisture sorption and loss at extremes of RH, and LOD at typical wet granulation drying conditions, and processability, i.e., corrosivity, and filming and/or sticking upon compression.
Topics: Antidepressive Agents; Chemistry, Pharmaceutical; Crystallization; Delayed-Action Preparations; Drug Stability; Humidity; Hydrochloric Acid; Isoquinolines; Logic; Phase Transition; Pyrroles; Solubility; Technology, Pharmaceutical; Temperature; Water
PubMed: 18431655
DOI: 10.1208/s12249-008-9068-2 -
Neuropsychopharmacologia Hungarica : a... Jun 2007Neuropsychopharmacology is dedicated to the study of the pathophysiology and treatment of mental pathology with the employment of centrally acting drugs. In... (Review)
Review
Neuropsychopharmacology is dedicated to the study of the pathophysiology and treatment of mental pathology with the employment of centrally acting drugs. In neuropsychopharmacological research the clinical effects of a psychotropic drug are linked to the effects of the substance on brain structures involved in its mode of action. It is assumed, that knowledge about the mode of action of a selectively effective psychotropic drug will provide clues about the pathophysiology of the illness, and conversely, that knowledge about the pathophysiology of an illness, will provide clues for developing clinically more effective psychotropic drugs. Since the currently employed clinical methodology for the demonstration of therapeutic efficacy links the mode of action of psychotropic drugs to pharmacologically heterogeneous populations, neuropsychopharmacological research does not provide the necessary feedback for developing more effective drugs. To resolve the pharmacological heterogeneity within currently used diagnoses, attempts were made to split syndrome-based psychiatric diagnoses into discrete neurobiological deficits, and to replace traditional psychiatric nosology by a genetic psychiatric nosology. Yet, to date, there is no alternative methodology to psychopathology-based psychiatric nosology for classifying mental pathology in a clinically relevant manner. As we are moving from the "neurotransmitter era" to a "genetic era" in neuropsychopharmacology, the need for identifying pharmacologically homogenous populations is becoming imminent. All primary targets of psychotropic drugs in the brain are encoded by genes which are identified, and any nosologic entity or psychiatric syndrome that corresponds with a treatment responsive population is a candidate for the generation of genetic hypotheses relevant to mental illness. Recognition that progress in neuropsychopharmacology, and molecular genetic research, depends on the speed clinical research can resolve the pharmacological heterogeneity within currently used diagnoses, led to the development of methodologies for the identification of treatment responsive form(s) of illness, such as the Composite Diagnostic Evaluation (CODE) System, and nosologic homotyping. The CODE System is a methodology for the identification of treatment responsive forms of illness if covered up by consensus-based diagnoses; it consists of a set of diagnostic algorithms that can assign simultaneously a diagnosis from several classifications to a patient. Nosologic homotypes are identical in elementary units of mental illness and are assigned the same position in the nosologic matrix, based on three "nosologic organizing principles. The empirically derived diagnostic categories are suitable for testing hypotheses relevant to the relationship between the "processing of mental events" and "signal transduction" in the central nervous system.
Topics: Biomedical Research; Depressive Disorder; Drug Design; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; Humans; Mental Disorders; Neuropharmacology; Neurotransmitter Agents; Psychiatric Status Rating Scales; Psychopharmacology; Psychotropic Drugs; Research Design; Severity of Illness Index
PubMed: 17970531
DOI: No ID Found -
The AAPS Journal Nov 2005This article examines the United States Pharmacopeia (USP) and its role in assessing the equivalence and inequivalence of biological and biotechnological drug substances... (Review)
Review
This article examines the United States Pharmacopeia (USP) and its role in assessing the equivalence and inequivalence of biological and biotechnological drug substances and products-a role USP has played since its founding in 1820. A public monograph in the United States Pharmacopeia-National Formulary helps practitioners and other interested parties understand how an article's strength, quality, and purity should be controlled. Such a monograph is a standard to which all manufactured ingredients and products should conform, and it is a starting point for subsequent-entry manufacturers, recognizing that substantial additional one-time characterization studies may be needed to document equivalence. Review of these studies is the province of the regulatory agency, but compendial tests can provide clarity and guidance in the process.
Topics: Biotechnology; Chemistry, Pharmaceutical; Dosage Forms; Humans; Pharmaceutical Preparations; Pharmacopoeias as Topic; Reference Standards; Therapeutic Equivalency; United States
PubMed: 16594632
DOI: 10.1208/aapsj070477 -
Ethno-diversity within current ethno-pharmacology as part of Israeli traditional medicine--a review.Journal of Ethnobiology and... Jan 2006The Holy Land has absorbed millions of immigrants in recent centuries: Jews from East and West, Druze, Circassians, Muslim and Christian Arabs. The land is unique and... (Review)
Review
The Holy Land has absorbed millions of immigrants in recent centuries: Jews from East and West, Druze, Circassians, Muslim and Christian Arabs. The land is unique and diverse in geographical location and ethnic groups, and also in its cultural characteristics, including traditional medicine and use of materia medica. However, these traditions have waned over the years. The young state of Israel adopted a "melting pot" approach to fashion Jews from all over the world into Israelis. The traditional medicine and materia medica of different ethnic groups (Yemenite, Iranian, and Iraqi Jews) are reviewed in this paper, as well as the ethno-botanical survey (first conducted in the 1980s, covering Bedouins, Druze, Circassians, and Muslim and Christian Arabs), and the matching ethno-pharmacological survey (conducted in the late 1990s) covering the medicines sold in stores. Present-day healers are usually not young and are believed to be the end of the chain of traditional medical knowledge. The ethno-diversity of Israel is becoming blurred; modernity prevails, and ethnic characteristics are fading. The characteristic lines of traditional medicine and materia medica have hardly lasted three generations. A salient former dividing line between ethnic groups, namely their use of different medicinal substances, paradoxically becomes a bridge for conservative users of all groups and religions. Shops selling these substances have become centers for "nostalgia" and preserving the oriental heritage, traditional medicine, and medicinal substances!
Topics: Animals; Cultural Diversity; Emigration and Immigration; Ethnopharmacology; Humans; Israel; Jews; Materia Medica; Medicine, Traditional; Minority Groups; Pharmaceutical Services; Plants, Medicinal; Religion and Medicine
PubMed: 16401348
DOI: 10.1186/1746-4269-2-4 -
The AAPS Journal Sep 2009Pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are transcription factors that control the expression of a broad array of genes involved not only in... (Review)
Review
Pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are transcription factors that control the expression of a broad array of genes involved not only in transcellular transport and biotransformation of many drugs, other xenochemicals, and endogenous substances, such as bile acid, bilirubin, and certain vitamins, but also in various physiological/pathophysiological processes such as lipid metabolism, glucose homeostasis, and inflammation. Ligands of PXR and CAR are chemicals of diverse structures, including naturally occurring compounds present in herbal medicines. The overall aim of this article is to provide an overview of our current understanding of the role of herbal medicines as modulators of PXR and CAR.
Topics: Animals; Constitutive Androstane Receptor; Herbal Medicine; Humans; Plants; Pregnane X Receptor; Rats; Receptors, Cytoplasmic and Nuclear; Receptors, Steroid
PubMed: 19688601
DOI: 10.1208/s12248-009-9135-y -
Molecules (Basel, Switzerland) Oct 2020Natural products are favored because of their non-toxicity, low irritants, and market reacceptance. We collected examples, according to ancient wisdom, of natural... (Review)
Review
Natural products are favored because of their non-toxicity, low irritants, and market reacceptance. We collected examples, according to ancient wisdom, of natural products to be applied in transdermal delivery. A transdermal delivery system, including different types of agents, such as ointments, patches, and gels, has long been used for skin concerns. In recent years, many novel transdermal applications, such as nanoemulsions, liposomes, lipid nanoparticles, and microneedles, have been reported. Nanosized drug delivery systems are widely applied in natural product deliveries. Nanosized materials notably enhance bioavailability and solubility, and are reported to improve the transdermal permeation of many substances compared with conventional topical formulations. Natural products have been made into nanosized biomaterials in order to enhance the penetration effect. Before introducing the novel transdermal applications of natural products, we present traditional methods within this article. The descriptions of novel transdermal applications are classified into three parts: liposomes, emulsions, and lipid nanoparticles. Each section describes cases that are related to promising natural product transdermal use. Finally, we summarize the outcomes of various studies on novel transdermal agents applied to skin treatments.
Topics: Administration, Cutaneous; Biological Products; Chemistry, Pharmaceutical; Drug Delivery Systems; Humans; Liposomes; Nanoparticles; Skin Absorption
PubMed: 33143260
DOI: 10.3390/molecules25215051