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Profiles of Drug Substances,... 2022A comprehensive profile of danazol describing the nomenclatures, formulae, elemental composition, appearance, uses and applications is presented. The profile contains...
A comprehensive profile of danazol describing the nomenclatures, formulae, elemental composition, appearance, uses and applications is presented. The profile contains the method which was utilized for the preparation of the drug substance and its respective scheme is outlined. The physical characteristics of the drug including the solubility, X-ray powder diffraction pattern, differential scanning calorimetry, thermal behavior and spectroscopic studies are described. The methods which were used for the analysis of the drug substance in bulk drug and/or in pharmaceutical formulations including the compendial, spectrophotometric, electrochemical and the chromatographic methods are reported. The stability, toxicity, pharmacokinetics, bioavailability, drug evaluation and monitoring, comparisons, pharmacology, in addition to several compiled reviews on the drug substance which were involved. Finally, two hundred and seventy-nine references are listed at the end of this profile.
Topics: Biological Availability; Danazol; Drug Compounding; Drug Stability; Solubility; X-Ray Diffraction
PubMed: 35396014
DOI: 10.1016/bs.podrm.2021.10.005 -
Profiles of Drug Substances,... 2020A comprehensive profile of piroxicam including the nomenclatures, formulae, elemental composition, appearance, uses and applications. The methods which were utilized for...
A comprehensive profile of piroxicam including the nomenclatures, formulae, elemental composition, appearance, uses and applications. The methods which were utilized for the preparation of the drug substance and their respective schemes are outlined. The physical characteristics of the drug including the ionization constant, solubility, x-ray powder diffraction pattern, differential scanning calorimetry, thermal behavior and spectroscopic studies are described. The methods which were used for the analysis of the drug substance in bulk drug and/or in pharmaceutical formulations including the compendial, spectrophotometric, electrochemical and the chromatographic methods are reported. The stability, toxicity, pharmacokinetics, bioavailability, drug evaluation, comparison, in addition to compiled reviews on the drug substance are involved. Finally, more than four hundred and fifty references are listed at the end of this profile.
Topics: Biological Availability; Drug Compounding; Drug Stability; Piroxicam; Solubility; X-Ray Diffraction
PubMed: 32164968
DOI: 10.1016/bs.podrm.2019.10.007 -
Profiles of Drug Substances,... 2018Ganciclovir is synthetic nucleoside analog of guanine closely related to acyclovir but has greater activity against cytomegalovirus. This comprehensive profile on... (Review)
Review
Ganciclovir is synthetic nucleoside analog of guanine closely related to acyclovir but has greater activity against cytomegalovirus. This comprehensive profile on ganciclovir starts with a description of the drug: nomenclature, formulae, chemical structure, elemental composition, and appearance. The uses and application of the drug are explained. The methods that were used for the preparation of ganciclovir are described and their respective schemes are outlined. The methods which were used for the physical characterization of the dug are: ionization constant, solubility, X-ray powder diffraction pattern, crystal structure, melting point, and differential scanning calorimetry. The chapter contains the spectra of the drug: ultraviolet spectrum, vibrational spectrum, nuclear magnetic resonance spectra, and the mass spectrum. The compendial methods of analysis of ganciclovir include the United States Pharmacopeia methods. Other methods of analysis that were reported in the literature include: high-performance liquid chromatography alone or with mass spectrometry, electrophoresis, spectrophotometry, voltammetry, chemiluminescence, and radioimmunoassay. Biological investigation on the drug includes: pharmacokinetics, metabolism, bioavailability, and biological analysis. Reviews on the methods used for preparation or for analysis of the drug are provided. The stability of the drug in various media and storage conditions is reported. More than 240 references are listed at the end of the chapter.
Topics: Animals; Antiviral Agents; Biological Availability; Biotransformation; Drug Compounding; Drug Stability; Ganciclovir; Humans; Technology, Pharmaceutical
PubMed: 29678260
DOI: 10.1016/bs.podrm.2017.12.001 -
Therapeutic Innovation & Regulatory... Sep 2019Pharmacometrics have advanced from compartmental analysis to noncompartmental analysis and population pharmacokinetics that require complicated mathematical programs....
Pharmacometrics have advanced from compartmental analysis to noncompartmental analysis and population pharmacokinetics that require complicated mathematical programs. These sophisticated mathematical analyses determine not only the usual pharmacometric measures of clearance and volume of distribution but also the effects of covariates on these measures. Although these analyses are very suitable to studies of small patient populations often encountered in pediatric studies, most pediatric clinicians have not been trained in how these analyses are conducted or the meaning of the results of these analyses expressed in terms of error measures and fixed and variable effects. In addition, clinicians may not be able to evaluate whether their patient population is adequately represented in the analysis. Thorough and clear descriptions of the methodology and the strengths and weaknesses of these analyses need to be published in journals read by clinicians.
Topics: Child; Clinical Trials as Topic; Humans; Models, Biological; Nonlinear Dynamics; Pediatrics; Pharmacokinetics; Research Design
PubMed: 31137952
DOI: 10.1177/2168479019851793 -
Journal of Clinical Pharmacology Feb 2022Population pharmacokinetic (popPK) approaches have spread widely throughout clinical pharmacology research, and every clinician should have some understanding of them.... (Review)
Review
Population pharmacokinetic (popPK) approaches have spread widely throughout clinical pharmacology research, and every clinician should have some understanding of them. After a general introduction on the fundamentals and fields of application of these approaches, this review focuses on parametric popPK methods to provide the clinicians with the conceptual tools to interpret appropriately the results of parametric popPK analyses and to understand their clinical utility. The emphasis is put on the clinical questions that popPK methods are best suited to address. The basic principles of the methodology are introduced first, and then the main algorithms and reference software programs used in such analyses are presented. The description of data analysis and clinical applications of the parametric popPK approach (ie, use in simulations and therapeutic drug monitoring) are illustrated with the example of the antiretroviral drug efavirenz.
Topics: Age Factors; Algorithms; Alkynes; Area Under Curve; Benzoxazines; Cyclopropanes; Humans; Metabolic Clearance Rate; Models, Biological; Models, Statistical; Pharmacokinetics; Sex Factors; Software Design
PubMed: 33103774
DOI: 10.1002/jcph.1633 -
Methods in Molecular Biology (Clifton,... 2021Intracellular drug metabolism involves transport, bioactivation, conjugation, and other biochemical steps. The dynamics of these steps are each dependent on a number of... (Review)
Review
Intracellular drug metabolism involves transport, bioactivation, conjugation, and other biochemical steps. The dynamics of these steps are each dependent on a number of other cellular factors that can ultimately lead to unexpected behavior. In this review, we discuss the confounding processes and coupled reactions within bioactivation networks that require a systems-level perspective in order to fully understand the time-varying behavior. When converting known in vitro characteristics of drug-enzyme interactions into descriptions of cellular systems, features such as substrate availability, cell-to-cell variability, and intracellular redox state, deserve special focus. Two examples are provided. First, a model of hydrogen peroxide clearance during chemotherapy treatment serves as a basis to discuss an example of sensitivity analysis. Second, an example of doxorubicin bioactivation is used for discussing points of consideration when constructing and analyzing network models of drug metabolism.
Topics: Doxorubicin; Drug Elimination Routes; Drug Therapy; Enzymes; Humans; Hydrogen Peroxide; Kinetics; Oxidation-Reduction; Systems Biology
PubMed: 34272703
DOI: 10.1007/978-1-0716-1554-6_15 -
Toxicology and Applied Pharmacology Jul 2021Perfluoropolyethers, also known as ether-PFAS, are linear or branched alkyl ether polymers, where the substituent hydrogens on the carbon atoms in the chain have been... (Review)
Review
Perfluoropolyethers, also known as ether-PFAS, are linear or branched alkyl ether polymers, where the substituent hydrogens on the carbon atoms in the chain have been fully replaced by fluorine atoms. Some of these molecules may have a carboxylate functional group attached to one of the terminal carbon atoms to form an ether-PFAS carboxylate. Perfluoropolyethers are used as processing aids in the manufacture of various types of perfluorinated polymeric materials which are used in a variety of consumer applications. Although the physicochemical and toxicological properties of certain perfluoropolyether compounds have been extensively studied, data are relatively sparse for some members of this class of compounds. Moreover, the physicochemical, toxicokinetic, and toxicological properties of ether-PFAS as a class have not been elucidated in previous comprehensive review articles. This article reviews the nomenclature and uses of ether-PFAS and compares the physicochemical properties, toxicokinetic characteristics, apical effects in toxicological studies, and dose-response profiles across four specific ether-PFAS compounds. This comparison, including a description of identified data gaps should help to inform the design of studies to further elucidate the characteristics of ether-PFAS and to propose potential read-across assessment strategies for members of this class.
Topics: Animals; Dose-Response Relationship, Drug; Environmental Pollutants; Ethers; Fluorocarbons; Humans; Molecular Structure; Risk Assessment; Structure-Activity Relationship; Toxicity Tests; Toxicokinetics
PubMed: 33933458
DOI: 10.1016/j.taap.2021.115531 -
Annales Pharmaceutiques Francaises May 2016Regarding the different disciplines that encompass the pharmacology and the toxicology, none is specifically dedicated to the description and analysis of the time-course... (Review)
Review
OBJECTIVES
Regarding the different disciplines that encompass the pharmacology and the toxicology, none is specifically dedicated to the description and analysis of the time-course of relevant toxic effects both in experimental and clinical studies. The lack of a discipline devoted to this major field in toxicology results in misconception and even in errors by clinicians.
MATERIAL AND METHODS
Review of the basic different disciplines that encompass pharmacology toxicology and comparing with the description of the time-course of effects in conditions in which toxicological analysis was not performed or with limited analytical evidence.
RESULTS
Review of the literature clearly shows how misleading is the current extrapolation of toxicokinetic data to the description of the time-course of toxic effects.
CONCLUSION
A new discipline entitled toxicodynetics should be developed aiming at a more systematic description of the time-course of effects in acute human and experimental poisonings. Toxicodynetics might help emergency physicians in risk assessment when facing a poisoning and contribute to a better assessment of quality control of data collected by poison control centres. Toxicodynetics would also allow a quantitative approach to the clinical effects resulting from drug-drug interaction.
Topics: Drug Overdose; Humans; Poison Control Centers; Risk Assessment; Specialization; Toxicokinetics; Toxicology
PubMed: 27107462
DOI: 10.1016/j.pharma.2016.02.003 -
The AAPS Journal Jul 2022The purpose of this study was to develop and validate a simultaneous dissolution and absorption testing tool, the "artificial gut simulator" (AGS), for oral drug...
The purpose of this study was to develop and validate a simultaneous dissolution and absorption testing tool, the "artificial gut simulator" (AGS), for oral drug formulations. The AGS was constructed using hollow fibers and housed in a 3-mL UV spectrophotometric cuvette that provided a large surface area-to-volume ratio to simulate absorption at a physiological rate. A quasi-steady-state model describing absorption was developed and validated using a high aqueous solubility, BCS-I model compound, caffeine. This model was used to optimize the AGS operating parameters to simulate physiological gastric emptying and caffeine absorption, which was further input into a one-compartment pharmacokinetic (PK) model. The in vivo caffeine plasma concentration-time profiles matched those predicted by the PK model with in vitro input from the AGS. This work provides a framework for establishing an in vitro/in vivo correlation with high-permeability, BCS-II supersaturating drug formulations, which will be explored in the future studies.
Topics: Administration, Oral; Caffeine; Gastrointestinal Absorption; Intestinal Absorption; Models, Biological; Permeability; Solubility
PubMed: 35879480
DOI: 10.1208/s12248-022-00721-1 -
Handbook of Experimental Pharmacology 2018This summarizing and descriptive review article is an update on previously published reviews. It covers English-written and PubMed-listed review articles and original... (Review)
Review
This summarizing and descriptive review article is an update on previously published reviews. It covers English-written and PubMed-listed review articles and original studies published between May 2016 and November 2017 on the toxicokinetics of new psychoactive substances (NPS). Compounds covered include stimulants and entactogens, synthetic cannabinoids, tryptamines, phenethylamine and phencyclidine-like drugs, benzodiazepines, and opioids. First, an overview and discussion is provided on selected review articles followed by an overview and discussion on selected original studies. Both sections are then concluded by an opinion on these latest developments. The present review shows that the NPS market is still highly dynamic and that studies regarding their toxicokinetics are necessary to understand risks associated with their consumption. Data collection and studies are encouraged to allow for detection of NPS in biological matrices in cases of acute intoxications or chronic consumption. Although some data are available, scientific papers dealing with the mechanistic reasons behind acute and chronic toxicity are still lacking.
Topics: Central Nervous System Stimulants; Humans; Illicit Drugs; Psychotropic Drugs; Substance-Related Disorders; Toxicokinetics
PubMed: 29476337
DOI: 10.1007/164_2018_102