Influence of Gegenqinlian Decoction on Pharmacokinetics and Pharmacodynamics of Atorvastatin Calcium in Hyperlipidemic Rats
AbstractBackground and ObjectivesGegenqinlian decoction (GQD), a classic traditional Chinese medicine (TCM), was described in Shanghan Lun. GQD is often combined with antihyperlipidemic drugs (mainly atrovastatin calcium) in TCM clinics. However, the herb-drug interaction between GQD and atrovastatin calcium (AC) is still unknown. To determine whether the combination is safe, we evaluated the effects of GQD on the activities of cytochrome P450 (CYP)  3A2 enzyme and investigated the impact of GQD on the pharmacokinetics and pharmacodynamics of AC in rats.MethodsThe pharmacokinetics of AC (10  mg/kg) with or withou...
Source: European Journal of Drug Metabolism and Pharmacokinetics - December 2, 2021 Category: Drugs & Pharmacology Source Type: research

Predictive Performance of Published Tacrolimus Population Pharmacokinetic Models in Thai Kidney Transplant Patients
AbstractBackground and ObjectiveTacrolimus is a narrow therapeutic index drug with high pharmacokinetic variability, and several tacrolimus population pharmacokinetic (PopPK) models were developed to guide individualized drug dosing. These models, however, may not perform well in other clinical settings. Therefore, we aimed to assess the predictive ability of published tacrolimus PopPK models using a dataset of Thai kidney transplant patients.MethodsThe external dataset was retrospectively collected from medical records of Bhumibol Adulyadej Hospital, Thailand. Published tacrolimus PopPK models were systematically searched...
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 24, 2021 Category: Drugs & Pharmacology Source Type: research

Andrographis paniculata Formulations: Impact on Diterpene Lactone Oral Bioavailability
AbstractDiterpene lactones have been identified as active compounds in several medicinal plants, includingAndrographis paniculata (Burm. f.) Nees, which is a medicinal plant that has been used for centuries across the world. Andrographolide is the major diterpene fromA. paniculata and the main bioactive constituent of this species. The effectiveness of diterpenes can be affected by factors that limit their oral bioavailability, such as their poor water solubility, slow dissolution rates, low gastrointestinal absorption, high chemical and metabolic instability, and rapid excretion. In this context, the purpose of the presen...
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 23, 2021 Category: Drugs & Pharmacology Source Type: research

Acknowledgement to Referees
(Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 10, 2021 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics of Vancomycin in Critically Ill Children: A Systematic Review
AbstractBackground  and ObjectiveVancomycin is often used in the ICU for the treatment of Gram-positive bacterial infection. In critically ill children, there are pathophysiologic changes that affect the pharmacokinetics of vancomycin. A systematic review of vancomycin pharmacokinetics  and pharmacodynamics in critically ill children was performed.MethodsPharmacokinetic studies of vancomycin in critically ill children published up to May 2021 were included in the review provided they included children aged> 1  month. Studies including neonates were excluded. A search was performed using the PubMed, Scopus...
Source: European Journal of Drug Metabolism and Pharmacokinetics - November 8, 2021 Category: Drugs & Pharmacology Source Type: research

Effects of Cytochrome P450 3A4 Induction and Inhibition on the Pharmacokinetics of BI 425809, a Novel Glycine Transporter 1 Inhibitor
ConclusionsSystemic exposure of BI 425809 was altered in the presence of strong CYP3A4 modulators, corroborating in vitro results that CYP3A4 mediates a major metabolic pathway for BI 425809.Trial Registration NumberNCT02342717 (registered on 15 January 2015) and NCT03082183 (registered on 10 March 2017) (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 29, 2021 Category: Drugs & Pharmacology Source Type: research

Pharmacology of Diosmin, a Citrus Flavone Glycoside: An Updated Review
AbstractFlavonoids are phytochemicals that are well known for their beneficial pharmacological properties. Diosmin is a flavone glycoside derived from hesperidin, a flavanone abundantly found in citrus fruits. Daflon is an oral phlebotonic flavonoid combination containing diosmin and hesperidin (9:1) that is commonly used for the management of blood vessel disorders. After oral administration, diosmin is converted to diosmetin, which is subsequently absorbed and esterified into glucuronide conjugates that are excreted in the urine. Pharmacological effects of diosmin have been investigated in several in vitro and in vivo st...
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 23, 2021 Category: Drugs & Pharmacology Source Type: research

A Drug –Drug Interaction Study to Investigate the Effect of Nintedanib on the Pharmacokinetics of Microgynon (Ethinylestradiol and Levonorgestrel) in Female Patients with Systemic Sclerosis-Associated Interstitial Lung Disease
ConclusionPharmacokinetic data indicate that there is no relevant effect of nintedanib on plasma exposure to ethinylestradiol and levonorgestrel in female patients with SSc-ILD.Trial RegistrationClinicaltrials.gov NCT03675581. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 18, 2021 Category: Drugs & Pharmacology Source Type: research

Impact of a High-Fat Meal and Sprinkled Administration on the Bioavailability and Pharmacokinetics of Viloxazine Extended-Release Capsules (QelbreeTM) in Healthy Adult Subjects
ConclusionsThese data suggest that viloxazine ER can be consumed sprinkled on applesauce or as intact capsules with or without meals without significantly changing its pharmacokinetics. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 15, 2021 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics and Pharmacodynamics of Huanglian-Houpo Decoction Based on Berberine Hydrochloride and Magnolol Against H1N1 Influenza Virus
ConclusionThe results indicated that berberine and magnolol are the main active ingredients of HH related to its anti-influenza virus effect, which is related to the improvement of IFN- β secretion. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 12, 2021 Category: Drugs & Pharmacology Source Type: research

Plasma Distribution of Methotrexate and Its Polyglutamates in Pediatric Acute Lymphoblastic Leukemia: Preliminary Insights
ConclusionThe presence of MTXPGs in plasma of patients with ALL could be related to the action of ABC efflux transporters on blood cells and hepatocytes resulting from the administration of high doses of methotrexate. This study may not draw definitive conclusions, but it does reduce uncertainty about the dynamics of methotrexate and its active metabolites, which may be of vital importance for achieving a clinical response. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 12, 2021 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics and Pharmacodynamics of Huanglian-Houpo Decoction Based on Berberine Hydrochloride and Magnolol Against H1N1 Influenza Virus
ConclusionThe results indicated that berberine and magnolol are the main active ingredients of HH related to its anti-influenza virus effect, which is related to the improvement of IFN- β secretion. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 12, 2021 Category: Drugs & Pharmacology Source Type: research

Plasma Distribution of Methotrexate and Its Polyglutamates in Pediatric Acute Lymphoblastic Leukemia: Preliminary Insights
ConclusionThe presence of MTXPGs in plasma of patients with ALL could be related to the action of ABC efflux transporters on blood cells and hepatocytes resulting from the administration of high doses of methotrexate. This study may not draw definitive conclusions, but it does reduce uncertainty about the dynamics of methotrexate and its active metabolites, which may be of vital importance for achieving a clinical response. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 12, 2021 Category: Drugs & Pharmacology Source Type: research

Single- and Multiple-Dose Pharmacokinetics and Safety of Vilaprisan in Healthy Postmenopausal Japanese Women: A Randomized Clinical Trial
ConclusionsOverall, vilaprisan was safe and well tolerated. The exposure in Japanese women was similar to that observed in European and Chinese women in separate studies.Trial Registration15 Nov 2011 (no registration number assigned). (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 11, 2021 Category: Drugs & Pharmacology Source Type: research

Association of Sofosbuvir and Daclatasvir Plasma Trough Concentrations with Patient-, Treatment-, and Disease-Related Factors Among HIV/HCV-Coinfected Persons
ConclusionsIn HIV/HCV-coinfected patients in a real-world setting, exposure to a high GS-331007 Ctrough was associated with a slight decrease in renal function, while advanced hepatic impairment was significantly associated with a lower daclatasvir Ctrough. Though the clinical and therapeutic relevance of these findings may be limited, increasing clinicians ’ knowledge regarding DAA exposure in difficult-to-treat patients could be relevant in single cases, and further investigations are warranted. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 8, 2021 Category: Drugs & Pharmacology Source Type: research

Population Pharmacokinetic Analysis from First-in-Human Data for HDAC Inhibitor, REC-2282 (AR-42), in Patients with Solid Tumors and Hematologic Malignancies: A Case Study for Evaluating Flat vs. Body Size Normalized Dosing
AbstractBackground and ObjectivesREC-2282  is a novel histone deacetylase inhibitor that has shown antitumor activity in in vitro and in vivo models of malignancy.  The aims of this study were to characterize the population pharmacokinetics of REC-2282 (AR-42) from the first-in-human (NCT01129193) and phase I acute myeloid leukemia tri als (NCT01798901) and to evaluate potential sources of variability. Additionally, we sought to understand alternate body size descriptors as sources of inter-individual variability (IIV), which was significant for dose-normalized maximum observed concentration and ar...
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 7, 2021 Category: Drugs & Pharmacology Source Type: research

Oral Antibiotics in Patients with Short Bowel Syndrome: Hurdles and Caveats
(Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - October 5, 2021 Category: Drugs & Pharmacology Source Type: research

Generic Drug Product Development in Japan: Regulatory Updates During 2014 –2019 and the Future
This report introduces the activities of the PMDA from fiscal years 2014 –2019. The number of approvals of new generic drug products and partial changes was trending downward. Alternatively, the PMDA conducted six types of consultation meetings to advise on development and application; the number of consultation meetings was increasing. Moreover, during this period, th e Ministry of Health, Labour and Welfare issued two basic principles for ophthalmic dosage forms and dry powder inhaler drug products and revised the guidelines for bioequivalence. Finally, the future of generic drug product development and considerati...
Source: European Journal of Drug Metabolism and Pharmacokinetics - September 29, 2021 Category: Drugs & Pharmacology Source Type: research

Correction to: Identifying Safety Thresholds for Immunosuppressive Drugs: Applying Insights from Primary Antibody Deficiencies to Mitigate Adverse Events in Secondary Antibody Deficiencies Using Mathematical Modeling of Preclinical and Early Clinical Data
(Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - September 28, 2021 Category: Drugs & Pharmacology Source Type: research

Severe 5-Fluorouracil-Associated Gastrointestinal Toxicity Unexplained by Dihydropyrimidine Dehydrogenase Deficiency and Renal Impairment: Should We Be Investigating Other Elimination Pathways to Assess the Risk of 5-Fluorouracil Toxicity?
(Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - September 27, 2021 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetic Properties of S-oxiracetam After Single and Multiple Intravenous Infusions in Healthy Volunteers
ConclusionsS-ORT was well tolerated, and no serious adverse events occurred in 2.0, 4.0 and 8.0 g in single- and 4.0 g in multiple-dose studies. S-ORT showed dose linearity with increasing doses and no drug accumulation after 7 days of continuous administration was observed. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - September 21, 2021 Category: Drugs & Pharmacology Source Type: research

Physiologically-Based Pharmacokinetic Modelling of Entrectinib Parent and Active Metabolite to Support Regulatory Decision-Making
ConclusionsThe model simulations were used to derive dosing recommendations for co-administering entrectinib with CYP3A4 inhibitors or inducers. PBPK modeling has been used in lieu of clinical studies to enable regulatory decision-making. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - September 8, 2021 Category: Drugs & Pharmacology Source Type: research

Oral Antibiotics in Patients with Short Bowel Syndrome: Do or Don ’t?
(Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - September 7, 2021 Category: Drugs & Pharmacology Source Type: research

Advances in Thiopurine Drug Delivery: The Current State-of-the-Art
AbstractThiopurines (mercaptopurine, azathioprine and thioguanine) are well-established maintenance treatments for a wide range of diseases such as leukemia, inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE) and other inflammatory and autoimmune diseases in general. Worldwide, millions of patients are treated with thiopurines. The use of thiopurines has been limited because of off-target effects such as myelotoxicity and hepatotoxicity. Therefore, seeking methods to enhance target-based thiopurine-based treatment is relevant, combined with pharmacogenetic testing. Controlled-release formulations for thio...
Source: European Journal of Drug Metabolism and Pharmacokinetics - September 6, 2021 Category: Drugs & Pharmacology Source Type: research

A Systematic Review of Multiple Linear Regression-Based Limited Sampling Strategies for Mycophenolic Acid Area Under the Concentration –Time Curve Estimation
ConclusionsThe review includes updated MPA LSSs, e.g., for different MPA formulations (suspension, dispersible tablets), generic form, and intravenous administration for adult and pediatric patients, and emphasizes the need of individual therapeutic approaches according to MMF indication. Five MLR-based MPA LSSs might be implemented into clinical practice after evaluation in independent groups of patients. Further studies are required, e.g., to establish fMPA LSS in pediatric patients. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - September 4, 2021 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics of Synthetic Cathinones Found in Bath Salts in Mouse Brain and Plasma Using High-Pressure Liquid Chromatography –Tandem Mass Spectrometry
ConclusionsThe pharmacokinetics of methylone, mepedrone, and MDPV are altered when the drugs are used in combination. These data provide insight into the consequences of co-exposure to synthetic cathinones in popular bath salt products. (Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - August 24, 2021 Category: Drugs & Pharmacology Source Type: research

Correction to: Bioavailability of a Capsaicin Lipid Multi ‑particulate Formulation in Rats
(Source: European Journal of Drug Metabolism and Pharmacokinetics)
Source: European Journal of Drug Metabolism and Pharmacokinetics - August 22, 2021 Category: Drugs & Pharmacology Source Type: research