Clinical Significance of the Plasma Protein Binding of Rifampicin in the Treatment of Tuberculosis Patients
(Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - July 22, 2019 Category: Drugs & Pharmacology Source Type: research

Exposure-Toxicity Relationships of Mycophenolic Acid in Adult Kidney Transplant Patients
AbstractMycophenolic acid is commonly prescribed in adult kidney transplant recipients for preventing graft rejection. A therapeutic target for total mycophenolic acid area under the concentration –time curve (30–60 mg h/L) has been established in adult kidney transplant recipients and widely referenced today. However, this specific target range does not adequately characterize mycophenolic acid-associated adverse effects. The primary objective of this qualitative and critical review wa s to characterize the exposure-toxicity relationships of mycophenolic acid in an attempt to determine whether exposu...
Source: Clinical Pharmacokinetics - July 22, 2019 Category: Drugs & Pharmacology Source Type: research

Population Pharmacokinetics of an Anti-PD-L1 Antibody, Durvalumab in Patients with Hematologic Malignancies
The objective of this study was to develop a population-pharmacokinetic model of durvalumab in patients with various hematologic malignancies and to investigate the effects of demographic and disease factors on the pharmacokinetics in this population.MethodsA total of 1812 concentrations from 267 patients with myelodysplastic syndromes, acute myeloid leukemia, multiple myeloma, non-Hodgkin lymphoma, or Hodgkin lymphoma were included in the analysis.ResultsThe pharmacokinetics of durvalumab was adequately described by a two-compartment model with first-order elimination. A decrease in durvalumab clearance over time was main...
Source: Clinical Pharmacokinetics - July 22, 2019 Category: Drugs & Pharmacology Source Type: research

What Antibiotic Exposures Are Required to Suppress the Emergence of Resistance for Gram-Negative Bacteria? A Systematic Review
ConclusionThe benefits of implementing such high PK/PD targets must be balanced with the potential risks of antibiotic-associated toxicity. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - July 20, 2019 Category: Drugs & Pharmacology Source Type: research

Population Pharmacokinetic Analysis of Fluticasone Furoate/Umeclidinium Bromide/Vilanterol in Patients with Chronic Obstructive Pulmonary Disease
ConclusionsAll FF, UMEC, and VI plasma concentrations were well interspersed with historical data and were all adequately described by a two-compartment model with first-order absorption. There were no clinically relevant differences in FF, UMEC, or VI systemic exposures when administered as FF/UMEC/VI, FF/VI  + UMEC, or the dual combinations FF/VI and/or UMEC/VI. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - July 19, 2019 Category: Drugs & Pharmacology Source Type: research

A Semi-Mechanistic Population Pharmacokinetic/Pharmacodynamic Model of Bortezomib in Pediatric Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia
ConclusionThe semi-physiological model adequately described the nonlinear PK and PD of bortezomib in plasma. This model can be used to further optimize dosing of bortezomib. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - July 16, 2019 Category: Drugs & Pharmacology Source Type: research

Reply to Periclou et al.: “Clinical Pharmacokinetics of Atypical Antipsychotics: An Update”
(Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - July 11, 2019 Category: Drugs & Pharmacology Source Type: research

Comment on: “Clinical Pharmacokinetics of Atypical Antipsychotics: An Update”
(Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - July 11, 2019 Category: Drugs & Pharmacology Source Type: research

Towards Personalized Antithrombotic Treatments: Focus on P2Y 12 Inhibitors and Direct Oral Anticoagulants
AbstractOral anticoagulants and antiplatelet drugs are commonly prescribed to lower the risk of cardiovascular diseases, such as venous and arterial thrombosis, which represent the leading causes of mortality worldwide. A significant percentage of patients taking antithrombotics will nevertheless experience bleeding or recurrent ischemic events, and this represents a major public health issue. Cardiovascular medicine is now questioning theone-size-fits-all policy, and more personalized approaches are increasingly being considered. However, the available tools are currently limited and they are only moderately able to predi...
Source: Clinical Pharmacokinetics - June 27, 2019 Category: Drugs & Pharmacology Source Type: research

Requirements to Establishing Confidence in Physiologically Based Pharmacokinetic (PBPK) Models and Overcoming Some of the Challenges to Meeting Them
AbstractWhen scientifically well-founded, the mechanistic basis of physiologically based pharmacokinetic (PBPK) models can help reduce the uncertainty and increase confidence in extrapolations outside the studied scenarios or studied populations. However, it is not always possible to establish mechanistically credible PBPK models. Requirements to establishing confidence in PBPK models, and challenges to meeting these requirements, are presented in this article. Parameter non-identifiability is the most challenging among the barriers to establishing confidence in PBPK models. Using case examples  of small molecule drug...
Source: Clinical Pharmacokinetics - June 25, 2019 Category: Drugs & Pharmacology Source Type: research

Correction to: Clinical Pharmacokinetics of Atypical Antipsychotics: An Update
The pharmacokinetics of CRP was tested in small short-term studies in both healthy volunteers and in subjects with schizophrenia, with similar results [242]. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - June 19, 2019 Category: Drugs & Pharmacology Source Type: research

Bayesian Population Model of the Pharmacokinetics of Venetoclax in Combination with Rituximab in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: Results from the Phase III MURANO Study
ConclusionsThe Bayesian model successfully characterized venetoclax PKs over time and confirmed key covariates affecting PKs in the MURANO study. The model was deemed appropriate for further use in simulations and for generating individual patient PK parameters for subsequent exposure –response evaluation. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - June 18, 2019 Category: Drugs & Pharmacology Source Type: research

Comment on “Levothyrox ® New and Old Formulations: Are They Switchable for Millions of Patients?”
(Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - June 12, 2019 Category: Drugs & Pharmacology Source Type: research

Comment on: Levothyrox ® New and Old Formulations: Are They Switchable for Millions of Patients?
(Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - June 12, 2019 Category: Drugs & Pharmacology Source Type: research

Authors ’ Reply to Castello-Bridoux et al.: “Comment on Levothyrox ® New and Old Formulations: Are they Switchable for Millions of Patients?”
(Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - June 12, 2019 Category: Drugs & Pharmacology Source Type: research

Author ’s Reply to Trechot: “Comment on Levothyrox ® New and Old Formulations: Are they Switchable for Millions of Patients?”
(Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - June 12, 2019 Category: Drugs & Pharmacology Source Type: research

Immune Checkpoint Inhibitors in Melanoma: A Review of Pharmacokinetics and Exposure –Response Relationships
AbstractImmune checkpoint inhibitors are a new class of monoclonal antibodies that amplify T-cell-mediated immune responses against cancer cells. The introduction of these new drugs, first anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4) and then anti-programmed death-1 (anti-PD1), was a major improvement in the treatment of advanced or metastatic melanoma, a highly immunogenic tumour. The development strategy for immune checkpoint immunotherapies differed from that traditionally used for cytotoxic therapies in oncology. The choices of doses at which to conduct clinical trials, and subsequently the choice of d...
Source: Clinical Pharmacokinetics - June 10, 2019 Category: Drugs & Pharmacology Source Type: research

Factors Contributing to Fentanyl Pharmacokinetic Variability Among Diagnostically Diverse Critically Ill Children
ConclusionsIn this study we show the feasibility and utility of using electronic record data and remnant blood samples to successfully construct population pharmacokinetic models for a heterogeneous cohort of critically ill children. A clinically relevant effect of concomitant CYP3A4/5 inducers was identified. Scaling this population pharmacokinetic approach is necessary to craft precision approaches to fentanyl administration for critically ill children. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - June 6, 2019 Category: Drugs & Pharmacology Source Type: research

Authors ’ Reply to Coste et al.: “Levothyrox ® New and Old Formulations: Are they Switchable for Millions of Patients?”
(Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - June 3, 2019 Category: Drugs & Pharmacology Source Type: research

Comment on: “Levothyrox ® New and Old Formulations: Are they Switchable for Millions of Patients?”
(Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - June 3, 2019 Category: Drugs & Pharmacology Source Type: research

Authors ’ Reply to Nicolas: “Levothyrox ® New and Old Formulations: Are they Switchable for Millions of Patients?”
(Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - June 3, 2019 Category: Drugs & Pharmacology Source Type: research

Population Pharmacokinetics of Alemtuzumab (Campath) in Pediatric Hematopoietic Cell Transplantation: Towards Individualized Dosing to Improve Outcome
ConclusionThe current practice with uniform milligram/kilogram doses leads to highly variable exposures in children due to the non-linear relationship between body weight and alemtuzumab PK. This model may be used for individualized dosing of alemtuzumab. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - May 27, 2019 Category: Drugs & Pharmacology Source Type: research

Phenotyping of Human CYP450 Enzymes by Endobiotics: Current Knowledge and Methodological Approaches
AbstractDrug response is subject to an important within- and between-individual variability owing, mainly, to pharmacokinetic and pharmacodynamic factors. Pharmacokinetics includes metabolism by cytochrome P450 (CYP450), major enzymes of phase I reactions that are responsible for the biotransformation of around 60% of the currently approved drugs. CYP450 activity and/or expression are influenced by multiple intrinsic and extrinsic factors, such as drug –drug interactions or genetic polymorphisms. Present phenotyping strategies with xenobiotics used to assess CYP450 activity could be replaced by less invasive procedur...
Source: Clinical Pharmacokinetics - May 27, 2019 Category: Drugs & Pharmacology Source Type: research

Physiologically Based Pharmacokinetic Models for Prediction of Complex CYP2C8 and OATP1B1 ( SLCO1B1 ) Drug –Drug–Gene Interactions: A Modeling Network of Gemfibrozil, Repaglinide, Pioglitazone, Rifampicin, Clarithromycin and Itraconazole
ConclusionsWhole-body PBPK models of gemfibrozil, repaglinide, and pioglitazone have been built and qualified for DDI and DGI prediction. PBPK modeling is applicable to investigate complex interactions between multiple drugs and genetic polymorphisms. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - May 25, 2019 Category: Drugs & Pharmacology Source Type: research

Unbound Fraction of Clozapine Significantly Decreases with Elevated Plasma Concentrations of the Inflammatory Acute-Phase Protein Alpha-1-Acid Glycoprotein
ConclusionsBoth the spiking experiment and patient study showed a significant association between elevated alpha-1-acid glycoprotein plasma concentrations and a lower clozapine unbound fraction. Future studies should include clinical data to examine whether this association is clinically relevant, suggesting any clozapine dose adjustments. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - May 21, 2019 Category: Drugs & Pharmacology Source Type: research

Viral Hepatitis C Therapy: Pharmacokinetic and Pharmacodynamic Considerations: A 2019 Update
AbstractIt has been estimated by the World Health Organization (WHO) that over 71  million people were infected with the hepatitis C virus (HCV) in 2015. Since then, a number of highly effective direct-acting antiviral (DAA) regimens have been licensed for the treatment of chronic HCV infection: sofosbuvir/daclatasvir, sofosbuvir/ledipasvir, elbasvir/grazoprevir, sofosbuvir/vel patasvir, glecaprevir/pibrentasvir, and sofosbuvir/velpatasvir/voxilaprevir. With these treatment regimens, almost all chronic HCV-infected patients, even including prior DAA failures, can be treated effectively and safely. It is therefore...
Source: Clinical Pharmacokinetics - May 21, 2019 Category: Drugs & Pharmacology Source Type: research

A Comprehensive Whole-Body Physiologically Based Pharmacokinetic Model of Dabigatran Etexilate, Dabigatran and Dabigatran Glucuronide in Healthy Adults and Renally Impaired Patients
ConclusionThis is the first implementation of a PBPK model for dabigatran to distinguish between the prodrug, active moiety, and main active metabolite. Following adjustment of the UGT2B15 metabolism and P-gp transport rates, the PBPK model accurately predicts the pharmacokinetics in renally impaired patients. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - May 18, 2019 Category: Drugs & Pharmacology Source Type: research

The Effect of Food Intake on the Pharmacokinetics of Oral Basal Insulin: A Randomised Crossover Trial in Healthy Male Subjects
AbstractBackgroundOral insulin 338 is a novel tablet formulation of a long-acting basal insulin. This randomised, open-label, four-period crossover trial investigated the effect of timing of food intake on the single-dose pharmacokinetic properties of oral insulin 338.MethodsAfter an overnight fast, 44 healthy males received single fixed doses of oral insulin 338 administered 0, 30, 60 or 360  min before consuming a standardised meal (500 kcal, 57 energy percent [E%] carbohydrate, 13 E% fat, 30 E% protein). Blood samples for pharmacokinetic assessment were taken up to 288 h post-dose.ResultsTo...
Source: Clinical Pharmacokinetics - May 16, 2019 Category: Drugs & Pharmacology Source Type: research

Clinical Pharmacokinetics and Pharmacodynamics of Transarterial Chemoembolization and Targeted Therapies in Hepatocellular Carcinoma
AbstractThe management of hepatocellular carcinoma (HCC) is based on a multidisciplinary decision tree. Treatment includes loco-regional therapy, mainly transarterial chemoembolization, for intermediate-stage HCC and systemic therapy with oral tyrosine kinase inhibitors (TKIs) for advanced HCC. Transarterial chemoembolization involves hepatic intra-arterial infusion with either conventional procedure or drug-eluting-beads. The aim of the loco-regional procedure is to deliver treatment as close as possible to the tumor both to embolize the tumor area and to enhance efficacy and minimize systemic toxicity of the anticancer d...
Source: Clinical Pharmacokinetics - May 15, 2019 Category: Drugs & Pharmacology Source Type: research

Apixaban: A Clinical Pharmacokinetic and Pharmacodynamic Review
AbstractApixaban is an oral, direct factor Xa inhibitor that inhibits both free and clot-bound factor Xa, and has been approved for clinical use in several thromboembolic disorders, including reduction of stroke risk in non-valvular atrial fibrillation, thromboprophylaxis following hip or knee replacement surgery, the treatment of deep vein thrombosis or pulmonary embolism, and prevention of recurrent deep vein thrombosis and pulmonary embolism. The absolute oral bioavailability of apixaban is  ~ 50%. Food does not have a clinically meaningful impact on the bioavailability. Apixaban exposure increases dose pr...
Source: Clinical Pharmacokinetics - May 14, 2019 Category: Drugs & Pharmacology Source Type: research

Population Pharmacokinetics of Sarilumab in Patients with Rheumatoid Arthritis
ConclusionsThese findings, combined with the safety and efficacy data, indicated limited clinical relevance of body-weight effect on sarilumab exposure. No adjustment in sarilumab dose is required for body weight or any other demographics assessed. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - May 4, 2019 Category: Drugs & Pharmacology Source Type: research

Population Pharmacokinetics of Mycophenolic Acid Co-Administered with Tacrolimus in Corticosteroid-Free Adult Kidney Transplant Patients
ConclusionsOur novel findings suggest the potential need to reduce mycophenolic acid dosage in subjects on corticosteroid-free regimens. Corticosteroid-free subjects may also be more sensitive to drug/gene interactions. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - May 4, 2019 Category: Drugs & Pharmacology Source Type: research

Population Pharmacokinetics of Risankizumab in Healthy Volunteers and Subjects with Moderate to Severe Plaque Psoriasis: Integrated Analyses of Phase I –III Clinical Trials
ConclusionRisankizumab is characterized by dose-proportional, bi-exponential disposition with no difference in exposure between healthy subjects and patients with psoriasis. None of the covariates identified as being statistically correlated with risankizumab CL has a clinically meaningful impact on its exposure with the proposed psoriasis clinical regimen of 150  mg administered SC at weeks 0 and 4, and every 12 weeks thereafter.ClinicalTrials.gov IdentifiersNCT01577550, NCT02054481, NCT02596217, NCT02684370, NCT02672852, NCT02684357, NCT02694523. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - May 4, 2019 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetic/Pharmacodynamic Modelling and Simulation of Lusutrombopag, a Novel Thrombopoietin Receptor Agonist, for the Treatment of Thrombocytopenia in Patients with Chronic Liver Disease Undergoing Invasive Procedures
ConclusionThe modelling and simulation support lusutrombopag 3 mg once daily for 7  days without platelet monitoring. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - May 4, 2019 Category: Drugs & Pharmacology Source Type: research

Clinical Pharmacokinetics and Pharmacodynamics of Eravacycline
AbstractOn 27 August, 2018, the US Food and Drug Administration approved eravacycline, a fluorocycline antimicrobial agent within the tetracycline class of antibacterial drugs, for the treatment of complicated intra-abdominal infections in patients aged 18  years and older. This decision was based on substantial clinical and pre-clinical data, including rigorous pharmacokinetic and pharmacodynamic work. This paper examines the in-vivo pharmacokinetic/pharmacodynamic work that led to the approval of eravacycline and explores how this important new ant ibiotic may be used to treat aggressive multidrug-resistant infectio...
Source: Clinical Pharmacokinetics - May 3, 2019 Category: Drugs & Pharmacology Source Type: research

Clinical Pharmacokinetics and Pharmacodynamics of Rifampicin in Human Tuberculosis
AbstractThe introduction of rifampicin (rifampin) into tuberculosis (TB) treatment five decades ago was critical for shortening the treatment duration for patients with pulmonary TB to 6  months when combined with pyrazinamide in the first 2 months. Resistance or hypersensitivity to rifampicin effectively condemns a patient to prolonged, less effective, more toxic, and expensive regimens. Because of cost and fears of toxicity, rifampicin was introduced at an oral daily dose of 600  mg (8–12 mg/kg body weight). At this dose, clinical trials in 1970s found cure rates of ≥ 95% and relapse rates of...
Source: Clinical Pharmacokinetics - May 3, 2019 Category: Drugs & Pharmacology Source Type: research

Comment on “Target-Controlled Continuous Infusion for Antibiotic Dosing: Proof-of-Principle in an In-silico Vancomycin Trial in Intensive Care Unit Patients”
(Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - May 2, 2019 Category: Drugs & Pharmacology Source Type: research

Calculation of the Coefficient of Variation of Log-Normally Distributed Parameter Values
(Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - April 30, 2019 Category: Drugs & Pharmacology Source Type: research

Predictive Value of Microdose Pharmacokinetics
AbstractPhase 0 microdose trials are exploratory studies to early assess human pharmacokinetics of new chemical entities, while limiting drug exposure and risks for participants. The microdose concept is based on the assumption that microdose pharmacokinetics can be extrapolated to pharmacokinetics of a therapeutic dose. However, it is unknown whether microdose pharmacokinetics are actually indicative of the pharmacokinetics at therapeutic dose. The aim of this review is to investigate the predictive value of microdose pharmacokinetics and to identify drug characteristics that may influence the scalability of these paramet...
Source: Clinical Pharmacokinetics - April 27, 2019 Category: Drugs & Pharmacology Source Type: research

A Prospective Clinical Study Characterizing the Influence of Morbid Obesity on the Pharmacokinetics of Gentamicin: Towards Individualized Dosing in Obese Patients
AbstractBackground and ObjectiveGentamicin is an aminoglycoside antibiotic predominantly used in bloodstream infections. Although the prevalence of obesity is increasing dramatically, there is no consensus on how to adjust the dose in obese individuals. In this prospective clinical study, we study the pharmacokinetics of gentamicin in morbidly obese and non-obese individuals to develop a dosing algorithm that results in adequate drug exposure across body weights.MethodsMorbidly obese subjects undergoing bariatric surgery and non-obese healthy volunteers received one intravenous dose of gentamicin (obese: 5  mg/kg base...
Source: Clinical Pharmacokinetics - April 24, 2019 Category: Drugs & Pharmacology Source Type: research

Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib
AbstractNintedanib is an oral, small-molecule tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis and patients with advanced non-small cell cancer of adenocarcinoma tumour histology. Nintedanib competitively binds to the kinase domains of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF). Studies in healthy volunteers and in patients with advanced cancer have shown that nintedanib has time-independent pharmacokinetic characteristics. Maximum plasma concentrations of nintedanib are reached approximately 2 –4 h afte...
Source: Clinical Pharmacokinetics - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Optimal Sampling Strategies for Therapeutic Drug Monitoring of First-Line Tuberculosis Drugs in Patients with Tuberculosis
AbstractBackgroundThe 24-h area under the concentration –time curve (AUC24)/minimal inhibitory concentration ratio is the best predictive pharmacokinetic/pharmacodynamic (PK/PD) parameter of the efficacy of first-line anti-tuberculosis (TB) drugs. An optimal sampling strategy (OSS) is useful for accurately estimating AUC24; however, OSS has not been developed in the fed state or in the early phase of treatment for first-line anti-TB drugs.MethodsAn OSS for the prediction of AUC24 of isoniazid, rifampicin, ethambutol and pyrazinamide was developed for TB patients starting treatment. A prospective, randomized, crossove...
Source: Clinical Pharmacokinetics - April 17, 2019 Category: Drugs & Pharmacology Source Type: research

Population Pharmacokinetics/Pharmacodynamics of Ticagrelor in Children with Sickle Cell Disease
ConclusionsThese analyses offer the first quantitative characterization of the dose-exposure-response relationship for ticagrelor in pediatric SCD patients. This model-based approach may be used to inform dose selection and design of subsequent studies that aim to define ticagrelor safety and efficacy in pediatric SCD patients. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - April 11, 2019 Category: Drugs & Pharmacology Source Type: research

Optimizing Estimated Glomerular Filtration Rate to Support Adult to Pediatric Pharmacokinetic Bridging Studies in Patients with Cystic Fibrosis
ConclusionsThe CKDEPI equation bridges PK data generated in adults to adolescents with CF better than the current regulatory standard. The eGFR should be expressed in absolute units (mL/min) for PK analyses. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - April 10, 2019 Category: Drugs & Pharmacology Source Type: research

Physicochemical Properties, Biotransformation, and Transport Pathways of Established and Newly Approved Medications: A Systematic Review of the Top 200 Most Prescribed Drugs vs. the FDA-Approved Drugs Between 2005 and 2016
ConclusionsThe higher portion of biologics in the newly approved drugs compared with the established list confirmed the growing demands for protein- and antibody-based therapies. Moreover, the larger number of hydrophilic drugs found in the newly approved list suggests that the probability of toxicity is likely to decrease. With regard to CYP-mediated major metabolism, CYP3A5 showed an increased involvement owing to the identification of unique probe substrates to differentiate CYP3As. Furthermore, the contribution of OATP1B1 and P-gp did not show a significant shift in the newly approved drugs as compared to the establish...
Source: Clinical Pharmacokinetics - April 10, 2019 Category: Drugs & Pharmacology Source Type: research

Assessment of Drug –Drug Interactions between Taspoglutide, a Glucagon-Like Peptide-1 Agonist, and Drugs Commonly Used in Type 2 Diabetes Mellitus: Results of Five Phase I Trials
ConclusionOverall, multiple doses of taspoglutide did not result in changes in the pharmacokinetics of digoxin, an oral contraceptive containing ethinylestradiol and levonorgestrel, lisinopril, warfarin, and simvastatin that would be considered of clinical relevance. Therefore, no dose adjustments are warranted upon co-administration. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - April 9, 2019 Category: Drugs & Pharmacology Source Type: research

Population Pharmacokinetic and Pharmacodynamic Analysis of GLPG1690, an Autotaxin Inhibitor, in Healthy Volunteers and Patients with Idiopathic Pulmonary Fibrosis
ConclusionBased on these results, 200 and 600  mg once-daily doses were selected for future clinical trials in patients with idiopathic pulmonary fibrosis. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - April 6, 2019 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics of the BCL-2 Inhibitor Venetoclax in Subjects with Hepatic Impairment
ConclusionsNo venetoclax dosage adjustment is required in subjects with mild or moderate hepatic impairment. In subjects with severe hepatic impairment, a 50% dose reduction of venetoclax is recommended to account for higher exposures and the longer half-life. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - April 5, 2019 Category: Drugs & Pharmacology Source Type: research

Levothyrox ® New and Old Formulations: Are they Switchable for Millions of Patients?
AbstractIn France, more than 2.5 million patients are currently treated with levothyroxine, mainly as the marketed product Levothyrox®. In March 2017, at the request of French authorities, a new formulation of Levothyrox® was licensed, with the objective of avoiding stability deficiencies of the old formulation. Before launching this new formulation, an average bioequivalence trial, based on European Union recommended guidelines, was performed. The implicit rationale was the assumption that the two products, being bioequivalent, would also be switchable, allowing substitution of the new for the old formulation, thu...
Source: Clinical Pharmacokinetics - April 4, 2019 Category: Drugs & Pharmacology Source Type: research