Number Of Pharmacokinetic Studies Research Articles

A One Health perspective on comparative cannabidiol and cannabidiolic acid pharmacokinetics and biotransformation in humans and domestic animals

The goal of pharmacokinetic (PK) studies is to provide a basis for appropriate dosing regimens with novel therapeutic agents. With a knowledge of the desired serum concentration for optimum pharmacological effect, the amount and rate of drug administration can be tailored to maintain that concentration based on the 24-hour PK modeling (eg, every 24 hours, every 12 hours) to achieve therapeutic ranges. This dosing and PK information are tailored to maintain that concentration. Typically, these optimum serum concentrations pertain across species. Single-dose PK modeling provides fundamental parameters to suggest dosing regimes. Multiple-dose PK studies provide information on steady-state serum levels to assure that desired therapeutic levels are maintained during chronic administration. Clinical trials using dosing suggested by these PK determinations provide proof that the compound is producing the desired therapeutic effect. A number of PK studies with cannabinoids in humans and domestic animals have been conducted with the goal of determining appropriate clinical use with these plant-derived products. The following review will focus on the PK of cannabidiol (CBD) and the lesser-known precursor of CBD, cannabidiolic acid (CBDA). Although Δ9-tetrahydrocannabinol (THC) has profound pharmacological effects and may be present at variable and potentially violative concentrations in hemp products, PK studies with THC will not be a major consideration. Because, in domestic animals, hemp-CBD products are usually administered orally, that route will be a focus. When available, PK results with CBD administered by other routes will be summarized. In addition, the metabolism of CBD across species appears to be different in carnivorous species compared with omnivorous/herbivorous species (including humans) based on current information, and the preliminary information related to this will be explained with the therapeutic implication being addressed in Currents in One Health by Ukai et al, JAVMA, May 2023.

Optimizing pharmacotherapy regimens in adult patients receiving extracorporeal membrane oxygenation: A narrative review for clinical pharmacists

AbstractExtracorporeal membrane oxygenation (ECMO) is a complex therapy aimed at providing mechanical support for patients with severe, life‐threating cardiac and/or respiratory failure. Research has demonstrated variability in pharmacokinetic changes in the critically ill patient population receiving ECMO. There is a need to understand the complexity of these pharmacokinetic changes to provide optimal pharmacotherapeutic regimens thereby maximizing effectiveness and mitigating harm. However, the number of pharmacokinetic studies in patients receiving ECMO remains small, and very few prospective studies have been published addressing optimal analgesic, sedative, or antimicrobial therapy. Anticoagulation is an additional important component of ECMO therapy but the preferred agent as well as dosing and monitoring strategy are unclear. The purpose of this narrative review is to discuss analgesia and sedation, antimicrobial, and anticoagulation management strategies in adult patients receiving ECMO.

Application of the <i>AlphaScreen</i> and <i>AlphaLisa</i> method in drug development and pharmacokinetic studies

Drug development requires high-tech, simple, and sensitive methods. AlphaLISA method was announced as a universal method that would fit the listed criteria. However, research of other works on the pharmacokinetics of drugs related to this method showed a small number of pharmacokinetic studies in clinical trials. In this review, we focused on not only the positive aspects of the Alpha method, but also its disadvantages.

Clinical pharmacology profile of vorinostat, a histone deacetylase inhibitor

Vorinostat is a histone deacetylase inhibitor that has demonstrated preclinical activity in numerous cancer models. Clinical activity has been demonstrated in patients with a variety of malignancies. Vorinostat is presently indicated for the treatment of patients with advanced cutaneous T cell lymphoma (CTCL). Clinical investigation is ongoing for therapy of other solid tumors and hematological malignancies either as monotherapy or in combination with other chemotherapeutic agents. This review summarizes the pharmacokinetic properties of vorinostat. Monotherapy pharmacokinetic data across a number of pharmacokinetic studies were reviewed, and data are presented. In addition, literature review was performed to obtain published Phase I and II pharmacokinetic combination therapy data to identify and characterize potential drug interactions with vorinostat. Pharmacokinetic data in special populations were also reviewed. The clinical pharmacology profile of vorinostat is favorable, exhibiting dose-proportional pharmacokinetics and modest food effect. There appear to be no major differences in the pharmacokinetics of vorinostat in special populations, including varying demographics and hepatic dysfunction. Combination therapy pharmacokinetic data indicate that vorinostat has a low propensity for drug interactions. Vorinostat's favorable clinical pharmacology and drug interaction profile aid in the ease of administration of vorinostat for the treatment of advanced CTCL and will be beneficial in continued assessment for other oncologic indications. Although a number of studies have been conducted to elucidate the detailed pharmacokinetic profile of vorinostat, more rigorous assessment of vorinostat pharmacokinetics, including clinical drug interaction studies, will be informative.

Pharmacokinetic Study of trans-Resveratrol in Adult Pigs

A number of pharmacokinetic studies have shown marked differences in the plasma metabolic profile of resveratrol (RES) between humans and animals and between individuals of the same species, which complicates the identification of the putative bioactive metabolites responsible for the beneficial effects of RES. On the basis of the physiological similarity between pigs and humans, the aim of this work was to characterize the metabolic profile and pharmacokinetics of RES in the plasma of pigs and to compare this to values reported in humans. RES (5.9 mg/kg of body weight) was orally administered to pigs. The following metabolites were identified in plasma using HPLC-MS/MS: RES-diglucuronide (1), two isomers of RES-sulfoglucuronide (2, 3), two isomers of RES-glucuronide (4, 5), RES-sulfate (6), and RES. The most abundant metabolites were 2, 5 (identified as resveratrol 3-O-glucuronide), and 6. The t(max) ranged from 0.9 h for compounds 2 and 5 to 2 h for compound 3. The highest C(max) value was 2223 ng/mL (5.5 μM) for metabolite 5, which was 2.6-, 3.3-, and 12-fold higher than that for metabolites 6, 2, and 3, respectively. Peak plasma levels of RES (53 ng/mL; 0.23 μM) were detected 0.5 h after RES ingestion. Apart from the low levels of RES aglycone, the RES metabolic profile in pigs differs from that found in humans. The identification of the actual active RES metabolites is a challenge that requires more complex studies which should take into account many possible influencing factors such as age, gender, and methodological approaches.

Bioavailability of dodeca-2E, 4E, 8E, 10E/Z-tetraenoic acid isobutylamides after oral administration in rats and distribution in various tissues

Background Preparations from Echinacea are among the best-selling phytopharmaceuticals worldwide and have been widely used for the treatment of common cold and various upper respiratory infections. The most relevant active principles of Echinacea extracts are alkamides, caffeic acid derivatives (CADs) and glycoproteins/polysaccharides [1]. The main alkamides in Echinacea preparations are the isomeric dodeca-2E,4E,8E,10E/Z-tetraenoic acid isobutylamides (''tetraenes''). Until now, a limited number of pharmacokinetic studies with alkamides have been reported, but no data exist about their distribution in tissues and transport through the blood-brain barrier (BBB). Therefore, we evaluated the pharmacokinetics of dodeca-2E,4E,8E,10E/Ztetraenoic acid isobutylamides after a single oral dose administration of 2.5 mg/kg in plasma as well as in liver and four different brain regions (hippocampus, cerebral cortex, striatum and cerebellum).

A novel method for the separation and quantitation of benzene metabolites using high-pressure liquid chromatography

A method for the separation of benzene metabolites using reverse-phase high-pressure liquid chromatography is described. The antoxidant, ascorbic acid is added to an aqueous mixture of 1,2,4-benzenetriol, hydroquinone, catechol, and phenol, to prevent autooxidation. The eluting solvents are equilibrated with nitrogen, degassed, and maintained under a nitrogen atmosphere during the analysis. A highly resolved and reproducible profile of the metabolites is achieved under these conditions. This method should prove useful in a number of pharmacokinetic studies where the biotransformation of the parent compound to autooxidizable species such as polyphenols and quinones precludes analysis under aerobic conditions.