Clinical Pharmacokinetics of Ponesimod, a Selective S1P1 Receptor Modulator, in the Treatment of Multiple Sclerosis
AbstractPonesimod, a selective, rapidly reversible, and orally active, sphingosine-1 phosphate receptor (S1P) modulator, is indicated for the treatment of relapsing –remitting multiple sclerosis (RRMS). The clinical pharmacokinetics (PK) and pharmacodynamics (PD) of ponesimod was studied in 16 phase I, one phase II, and one phase III clinical studies. Ponesimod population PK was characterized by an open two-compartment disposition model with a terminal half-l ife of 33 h (accumulation factor of 2- to 2.6-fold), and fast and almost complete oral absorption (absolute oral bioavailability: 84%), reaching peak plasma and bl...
Source: Clinical Pharmacokinetics - September 30, 2023 Category: Drugs & Pharmacology Source Type: research

Escitalopram and Sertraline Population Pharmacokinetic Analysis in Pediatric Patients
ConclusionTo our knowledge, this is the largest population PK analysis of escitalopram and sertraline in pediatric patients. Significant PK variability for both medications was observed and was largely explained by CYP2C19 phenotype. Slower CYP2C19 metabolizers taking escitalopram or sertraline may benefit from dose reductions given increased exposure. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - September 27, 2023 Category: Drugs & Pharmacology Source Type: research

Comment on: Evaluation of the Influence of Sildenafil on the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Vericiguat in Healthy Adults
(Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - September 26, 2023 Category: Drugs & Pharmacology Source Type: research

Authors ’ Reply to Ganijee et al.: “Comment on: Evaluation of the Influence of Sildenafil on Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Vericiguat in Healthy Adults”
(Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - September 26, 2023 Category: Drugs & Pharmacology Source Type: research

Comment on: Evaluation of the Influence of Sildenafil on the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Vericiguat in Healthy Adults
(Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - September 26, 2023 Category: Drugs & Pharmacology Source Type: research

Authors ’ Reply to Ganijee et al.: “Comment on: Evaluation of the Influence of Sildenafil on Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Vericiguat in Healthy Adults”
(Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - September 26, 2023 Category: Drugs & Pharmacology Source Type: research

Cannabidiol Exposure Through Maternal Marijuana Use: Predictions in Breastfed Infants
ConclusionsBased on real-world use, breastfeeding infants are predicted to receive very small exposures of CBD through milk. Studies examining adverse reactions will provide further insight into potential risk. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - September 21, 2023 Category: Drugs & Pharmacology Source Type: research

Mechanisms and Clinical Significance of Pharmacokinetic Drug Interactions Mediated by FDA and EMA-approved Hepatitis C Direct-Acting Antiviral Agents
AbstractThe treatment of patients infected with the hepatitis C virus (HCV) has been revolutionised by the development of direct-acting antiviral agents (DAAs) that target specific HCV proteins involved in viral replication. The first DAAs were associated with clinical problems such as adverse drug reactions and pharmacokinetic drug –drug interactions (DDIs). Current FDA/EMA-approved treatments are combinations of DAAs that simultaneously target the HCV N5A-protein, the HCV N5B-polymerase and the HCV NS3/4A-protease. Adverse events and DDIs are less likely with these DAA combinations but several DDIs of potential clinica...
Source: Clinical Pharmacokinetics - September 20, 2023 Category: Drugs & Pharmacology Source Type: research

Multivariate Exact Discrepancy: A New Tool for PK/PD Model Evaluation
ConclusionWe propose a straightforward method for evaluating models during their development and selecting a model to perform therapeutic drug monitoring. Based on our preliminary results, the method is very promising but needs to be validated on a larger scale. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - September 17, 2023 Category: Drugs & Pharmacology Source Type: research

Irinotecan-Induced Toxicity: A Pharmacogenetic Study Beyond UGT1A1
ConclusionOur study indicates thatABCG2 andCES1 SNPs might be used as predictive markers for irinotecan-induced toxicity. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - September 16, 2023 Category: Drugs & Pharmacology Source Type: research