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Journal of Clinical Pharmacology Oct 2018Effective drug therapy to optimally influence disease requires an understanding of a drug's pharmacokinetic, pharmacodynamic, and pharmacogenomic interrelationships. In... (Review)
Review
Effective drug therapy to optimally influence disease requires an understanding of a drug's pharmacokinetic, pharmacodynamic, and pharmacogenomic interrelationships. In pediatrics, age is a continuum that can and does add variability in drug disposition and effect. This article addresses the many important factors that influence drug disposition and effect relative to age. What is known about the influence of maturation on the processes of drug absorption, distribution, metabolism, excretion, and drug receptor dynamics are outlined. Our state of understanding of many of these factors remains in flux, however, and only with additional study will we be able to better anticipate and model drug-response relationships across the age continuum. Being able to continuously improve our care of the ill pediatric patient while simultaneously being able to accurately determine the utility of new drugs and chemical entities in this population requires our enhanced understanding of these disposition characteristics.
Topics: Aging; Child; Child Development; Humans; Intestinal Absorption; Kidney; Pharmaceutical Preparations; Pharmacokinetics; Pharmacological Phenomena; Tissue Distribution
PubMed: 30248190
DOI: 10.1002/jcph.1284 -
Marine Drugs Nov 2020Marine organisms represent an excellent source of innovative compounds that have the potential for the development of new drugs. The pharmacokinetics of marine drugs has... (Review)
Review
Marine organisms represent an excellent source of innovative compounds that have the potential for the development of new drugs. The pharmacokinetics of marine drugs has attracted increasing interest in recent decades due to its effective and potential contribution to the selection of rational dosage recommendations and the optimal use of the therapeutic arsenal. In general, pharmacokinetics studies how drugs change after administration via the processes of absorption, distribution, metabolism, and excretion (ADME). This review provides a summary of the pharmacokinetics studies of marine-derived active compounds, with a particular focus on their ADME. The pharmacokinetics of compounds derived from algae, crustaceans, sea cucumber, fungus, sea urchins, sponges, mollusks, tunicate, and bryozoan is discussed, and the pharmacokinetics data in human experiments are analyzed. In-depth characterization using pharmacokinetics is useful for obtaining information for understanding the molecular basis of pharmacological activity, for correct doses and treatment schemes selection, and for more effective drug application. Thus, an increase in pharmacokinetic research on marine-derived compounds is expected in the near future.
Topics: Animals; Aquatic Organisms; Biological Availability; Biological Products; Drug Dosage Calculations; Half-Life; Humans; Metabolic Clearance Rate; Tissue Distribution
PubMed: 33182407
DOI: 10.3390/md18110557 -
British Journal of Clinical Pharmacology Mar 2015A number of anatomical and physiological factors determine the pharmacokinetic profile of a drug. Differences in physiology in paediatric populations compared with... (Review)
Review
A number of anatomical and physiological factors determine the pharmacokinetic profile of a drug. Differences in physiology in paediatric populations compared with adults can influence the concentration of drug within the plasma or tissue. Healthcare professionals need to be aware of anatomical and physiological changes that affect pharmacokinetic profiles of drugs to understand consequences of dose adjustments in infants and children. Pharmacokinetic clinical trials in children are complicated owing to the limitations on blood sample volumes and perception of pain in children resulting from blood sampling. There are alternative sampling techniques that can minimize the invasive nature of such trials. Population based models can also limit the sampling required from each individual by increasing the overall sample size to generate robust pharmacokinetic data. This review details key considerations in the design and development of paediatric pharmacokinetic clinical trials.
Topics: Child; Clinical Trials as Topic; Humans; Inactivation, Metabolic; Intestinal Absorption; Models, Biological; Pediatrics; Pharmaceutical Preparations; Pharmacokinetics; Tissue Distribution
PubMed: 25855821
DOI: 10.1111/bcp.12267 -
Nutrients Sep 2019The yellow pigment curcumin, extracted from turmeric, is a renowned polyphenol with a broad spectrum of health properties such as antioxidant, anti-inflammatory,... (Review)
Review
The yellow pigment curcumin, extracted from turmeric, is a renowned polyphenol with a broad spectrum of health properties such as antioxidant, anti-inflammatory, anti-cancer, antidiabetic, hepatoprotective, anti-allergic, anti-dermatophyte, and neuroprotective. However, these properties are followed by a poor pharmacokinetic profile which compromises its therapeutic potential. The association of low absorption by the small intestine and the extensive reductive and conjugative metabolism in the liver dramatically weakens the oral bioavailability. Several strategies such as inhibition of curcumin metabolism with adjuvants as well as novel solid and liquid oral delivery systems have been tried to counteract curcumin poor absorption and rapid elimination from the body. Some of these drug deliveries can successfully enhance the solubility, extending the residence in plasma, improving the pharmacokinetic profile and the cellular uptake.
Topics: Biological Availability; Curcuma; Curcumin; Drug Delivery Systems; Humans; Intestinal Absorption; Intestine, Small; Liver; Solubility
PubMed: 31500361
DOI: 10.3390/nu11092147 -
European Journal of Pharmaceutical... Jun 2019The simultaneous intake of food and drugs can have a strong impact on drug release, absorption, distribution, metabolism and/or elimination and consequently, on the... (Review)
Review
The simultaneous intake of food and drugs can have a strong impact on drug release, absorption, distribution, metabolism and/or elimination and consequently, on the efficacy and safety of pharmacotherapy. As such, food-drug interactions are one of the main challenges in oral drug administration. Whereas pharmacokinetic (PK) food-drug interactions can have a variety of causes, pharmacodynamic (PD) food-drug interactions occur due to specific pharmacological interactions between a drug and particular drinks or food. In recent years, extensive efforts were made to elucidate the mechanisms that drive pharmacokinetic food-drug interactions. Their occurrence depends mainly on the properties of the drug substance, the formulation and a multitude of physiological factors. Every intake of food or drink changes the physiological conditions in the human gastrointestinal tract. Therefore, a precise understanding of how different foods and drinks affect the processes of drug absorption, distribution, metabolism and/or elimination as well as formulation performance is important in order to be able to predict and avoid such interactions. Furthermore, it must be considered that beverages such as milk, grapefruit juice and alcohol can also lead to specific food-drug interactions. In this regard, the growing use of food supplements and functional food requires urgent attention in oral pharmacotherapy. Recently, a new consortium in Understanding Gastrointestinal Absorption-related Processes (UNGAP) was established through COST, a funding organisation of the European Union supporting translational research across Europe. In this review of the UNGAP Working group "Food-Drug Interface", the different mechanisms that can lead to pharmacokinetic food-drug interactions are discussed and summarised from different expert perspectives.
Topics: Administration, Oral; Biological Availability; Drug Liberation; Europe; Food-Drug Interactions; Gastrointestinal Absorption; Gastrointestinal Tract; Humans; Intestinal Absorption; Pharmacokinetics
PubMed: 30974173
DOI: 10.1016/j.ejps.2019.04.003 -
Drug Metabolism and Pharmacokinetics Feb 2019Over the past few decades, monoclonal antibodies (mAbs) have become one of the most important and fastest growing classes of therapeutic molecules, with applications in... (Review)
Review
Over the past few decades, monoclonal antibodies (mAbs) have become one of the most important and fastest growing classes of therapeutic molecules, with applications in a wide variety of disease areas. As such, understanding of the determinants of mAb pharmacokinetic (PK) processes (absorption, distribution, metabolism, and elimination) is crucial in developing safe and efficacious therapeutics. In the present review, we discuss the use of physiologically-based pharmacokinetic (PBPK) models as an approach to characterize the in vivo behavior of mAbs, in the context of the key PK processes that should be considered in these models. Additionally, we discuss current and potential future applications of PBPK in the drug discovery and development timeline for mAbs, spanning from identification of potential target molecules to prediction of potential drug-drug interactions. Finally, we conclude with a discussion of currently available PBPK models for mAbs that could be implemented in the drug development process.
Topics: Animals; Antibodies, Monoclonal; Drug Development; Drug Discovery; Humans; Models, Biological; Tissue Distribution
PubMed: 30522890
DOI: 10.1016/j.dmpk.2018.11.002 -
Biological Trace Element Research Jan 2019Magnesium is an element of great importance functioning because of its association with many cellular physiological functions. The magnesium content of foods is...
Magnesium is an element of great importance functioning because of its association with many cellular physiological functions. The magnesium content of foods is gradually decreasing due to food processing, and magnesium supplementation for healthy living has become increasingly popular. However, data is very limited on the bioavailability of various magnesium preparations. The aim of this study is to investigate the bioavailability of five different magnesium compounds (magnesium sulfate, magnesium oxide, magnesium acetyl taurate, magnesium citrate, and magnesium malate) in different tissues. Following a single dose 400 mg/70 kg magnesium administration to Sprague Dawley rats, bioavailability was evaluated by examining time-dependent absorption, tissue penetration, and the effects on the behavior of the animals. Pharmacokinetically, the area under the curve calculation is highest in the magnesium malate. The magnesium acetyl taurate was found to have the second highest area under the curve calculation. Magnesium acetyl taurate was rapidly absorbed, able to pass through to the brain easily, had the highest tissue concentration level in the brain, and was found to be associated with decreased anxiety indicators. Magnesium malate levels remained high for an extended period of time in the serum. The commonly prescribed dietary supplements magnesium oxide and magnesium citrate had the lowest bioavailability when compared to our control group. More research is needed to investigate the bioavailability of magnesium malate and acetyl taurate compounds and their effects in specific tissues and on behavior.
Topics: Animals; Area Under Curve; Biological Availability; Dietary Supplements; Magnesium Compounds; Male; Rats; Rats, Sprague-Dawley; Time Factors
PubMed: 29679349
DOI: 10.1007/s12011-018-1351-9 -
Clinical Drug Investigation Oct 2015Previously published studies have suggested the lack of a pharmacokinetic interaction between ibuprofen and paracetamol when they are delivered as a fixed-dose oral... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
Previously published studies have suggested the lack of a pharmacokinetic interaction between ibuprofen and paracetamol when they are delivered as a fixed-dose oral combination. The aim of this study was to determine the pharmacokinetic profile and safety of a fixed-dose intravenous (IV) combination, containing 3 mg/mL ibuprofen and 10 mg/mL paracetamol, in comparison with its individual components. The study also assessed the relative bioavailability of the same doses of the active ingredients when they were administered as an oral formulation.
METHODS
A single-dose, open-label, randomized, five-period cross-over sequence pharmacokinetic study was undertaken in 30 healthy volunteers. Serial plasma samples were assayed for both paracetamol and ibuprofen concentrations, using validated liquid chromatography-tandem mass spectrometry methods. Pharmacokinetic parameters were computed using standard non-compartmental analyses. Adverse events were also assessed. The ratios of the maximum measured plasma concentration (C max), the area under the plasma concentration-time curve (AUC) from time zero to the time of the last measurable plasma concentration (AUCt ) and AUC from time zero to infinity (AUC∞) were analysed for bioequivalence as determined by 90% confidence intervals.
RESULTS
The pharmacokinetic parameters of ibuprofen and paracetamol were very similar for the combination and monotherapy IV preparations; the ratios of the C max, AUC t and AUC∞ values fell within the 80-125% acceptable bioequivalence range. Precise dose proportionality for both compounds was also determined for the half dose of the IV formulation in comparison with the full dose. The relative bioavailability of paracetamol (93.78%) and ibuprofen (96.45%) confirmed the pharmacokinetic equivalence of the oral and IV formulations of the fixed-dose combination.
CONCLUSION
Concomitant administration of 3 mg/mL ibuprofen and 10 mg/mL paracetamol in a fixed-dose IV combination does not alter the pharmacokinetic profiles of either drug. The IV and oral dose forms of such a combination are pharmacokinetically equivalent.
Topics: Acetaminophen; Administration, Intravenous; Administration, Oral; Adolescent; Adult; Area Under Curve; Biological Availability; Cross-Over Studies; Drug Combinations; Female; Healthy Volunteers; Humans; Ibuprofen; Male; Middle Aged; Therapeutic Equivalency; Young Adult
PubMed: 26334726
DOI: 10.1007/s40261-015-0320-8 -
Journal of Clinical Pharmacology Feb 2020Target-mediated drug disposition (TMDD) is a term to describe a nonlinear pharmacokinetic (PK) phenomenon that is caused by high-affinity binding of a compound to its... (Review)
Review
Target-mediated drug disposition (TMDD) is a term to describe a nonlinear pharmacokinetic (PK) phenomenon that is caused by high-affinity binding of a compound to its pharmacologic targets. As the interaction between a drug and its pharmacologic target belongs to the process of pharmacodynamics (PD), TMDD can be viewed as a consequence of "PD affecting PK." Although there are numerous TMDD-related articles in the literature, most of them focus on characterizing TMDD using various mathematical models, which may not be suitable for those readers who have little interest in mathematical modeling and only want to have an understanding of the basic concept. The goal of this review is to serve as a "primer" on TMDD. This review explains (1) how TMDD happens; (2) why large-molecule and small-molecule compounds exhibiting TMDD demonstrate substantially different nonlinear PK behaviors; (3) what nonlinear PK profiles look like in large-molecule and small-molecule compounds exhibiting TMDD, using pegfilgrastim, erythropoietin, ABT-384, and linagliptin as case examples; and (4) how to identify whether the nonlinear PK of a compound is because of TMDD.
Topics: Animals; Drug Delivery Systems; Humans; Nonlinear Dynamics; Pharmaceutical Preparations; Pharmacokinetics; Tissue Distribution
PubMed: 31793004
DOI: 10.1002/jcph.1545 -
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