Clinical Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Anifrolumab
AbstractThe type I interferon (IFN) signaling pathway is implicated in the pathogenesis of systemic lupus erythematosus (SLE). Anifrolumab is a monoclonal antibody that targets the type I IFN receptor subunit 1. Anifrolumab is approved in several countries for patients with moderate to severe SLE receiving standard therapy. The approved dosing regimen of anifrolumab is a 300-mg dose administered intravenously every 4 weeks; this was initially based on the results of the Phase 2b MUSE and further confirmed in the Phase 3 TULIP-1 and TULIP-2 trials, in which anifrolumab 300-mg treatment was associated with clinically meaning...
Source: Clinical Pharmacokinetics - May 6, 2023 Category: Drugs & Pharmacology Source Type: research
Estimation of FMO3 Ontogeny by Mechanistic Population Pharmacokinetic Modelling of Risdiplam and Its Impact on Drug –Drug Interactions in Children
ConclusionMech-PPK modelling successfully estimated in vivo FMO3 ontogeny from risdiplam data collected from 525 subjects aged 2 months –61 years. To our knowledge, this is the first investigation of in vivo FMO3 ontogeny by population approach using comprehensive data covering a wide age range. Derivation of a robust in vivo FMO3 ontogeny function has significant implications on the prospective prediction of PK and DDI in childr en for other FMO3 substrates in the future, as illustrated in the current study for FMO3 and/or dual CYP3A-FMO3 substrates.Clinical Trial Registry NumbersNCT02633709, NCT03032172, NCT02908685, ...
Source: Clinical Pharmacokinetics - May 6, 2023 Category: Drugs & Pharmacology Source Type: research
Clinical Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Anifrolumab
AbstractThe type I interferon (IFN) signaling pathway is implicated in the pathogenesis of systemic lupus erythematosus (SLE). Anifrolumab is a monoclonal antibody that targets the type I IFN receptor subunit 1. Anifrolumab is approved in several countries for patients with moderate to severe SLE receiving standard therapy. The approved dosing regimen of anifrolumab is a 300-mg dose administered intravenously every 4 weeks; this was initially based on the results of the Phase 2b MUSE and further confirmed in the Phase 3 TULIP-1 and TULIP-2 trials, in which anifrolumab 300-mg treatment was associated with clinically meaning...
Source: Clinical Pharmacokinetics - May 6, 2023 Category: Drugs & Pharmacology Source Type: research
Association Between Clozapine Plasma Concentrations and Treatment Response: A Systematic Review, Meta-analysis and Individual Participant Data Meta-analysis
ConclusionsOur work confirmed that, in contrast to clozapine doses, clozapine plasma concentrations were related to a favourable clinical response, with a mean difference between responders and non-responders of 117 ng/mL. A threshold for a treatment response of 407 ng/mL was determined, with a high discriminatory capacity, and a sensitivity and specificity of 71% and 89.1%, respectively. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - May 5, 2023 Category: Drugs & Pharmacology Source Type: research
Comparison of Three Renal Function Formulas for Ganciclovir/Valganciclovir Dose Individualization in CMV-Infected Solid Organ Transplantation Patients Using a Population Approach
ConclusionsThe model based on the more accurate estimation of the renal function with the CKD-EPI formula and body weight as a size metric most used in the clinical practice can refine initial dose recommendations and contribute to GCV and VGCV dose individualization when required in the prevention or treatment of cytomegalovirus infection in solid organ transplantation patients.Graphical Abstract (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - May 4, 2023 Category: Drugs & Pharmacology Source Type: research
Multicenter Population Pharmacokinetics and Exposure –Efficacy Analysis of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis
ConclusionsIn patients with IPF, covariates such as bodyweight and food might not be sufficient for dose adjustment, and a low dose of 1500 mg/day could also provide 80% of theEmax, as the standard dose (1800 mg/day). (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - May 4, 2023 Category: Drugs & Pharmacology Source Type: research
Pharmacokinetics and Safety of Cotadutide, a GLP-1 and Glucagon Receptor Dual Agonist, in Individuals with Renal Impairment: A Single-Dose, Phase I, Bridging Study
ConclusionsThese results suggest that the PK and tolerability of cotadutide are unaffected by renal function and that dose adjustments may not be required in individuals with renal impairment. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - May 4, 2023 Category: Drugs & Pharmacology Source Type: research
Multicenter Population Pharmacokinetics and Exposure –Efficacy Analysis of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis
ConclusionsIn patients with IPF, covariates such as bodyweight and food might not be sufficient for dose adjustment, and a low dose of 1500 mg/day could also provide 80% of theEmax, as the standard dose (1800 mg/day). (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - May 4, 2023 Category: Drugs & Pharmacology Source Type: research
Comparison of Three Renal Function Formulas for Ganciclovir/Valganciclovir Dose Individualization in CMV-Infected Solid Organ Transplantation Patients Using a Population Approach
ConclusionsThe model based on the more accurate estimation of the renal function with the CKD-EPI formula and body weight as a size metric most used in the clinical practice can refine initial dose recommendations and contribute to GCV and VGCV dose individualization when required in the prevention or treatment of cytomegalovirus infection in solid organ transplantation patients.Graphical Abstract (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - May 4, 2023 Category: Drugs & Pharmacology Source Type: research
Pharmacokinetics and Safety of Cotadutide, a GLP-1 and Glucagon Receptor Dual Agonist, in Individuals with Renal Impairment: A Single-Dose, Phase I, Bridging Study
ConclusionsThese results suggest that the PK and tolerability of cotadutide are unaffected by renal function and that dose adjustments may not be required in individuals with renal impairment. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - May 4, 2023 Category: Drugs & Pharmacology Source Type: research
Clinical Pharmacokinetics and Pharmacodynamics of Voclosporin
AbstractVoclosporin is an approved option for the long-term treatment of lupus nephritis. We aimed to provide a narrative review of the pharmacokinetics and pharmacodynamics of voclosporin. In addition, we derived values for pharmacokinetic and pharmacodynamic parameters by graphical analysis of published diagrams. Compared with cyclosporin, low-dose voclosporin is associated with a lower nephrotoxicity risk and, compared to tacrolimus, with a lower diabetes risk. After repetitive dosing of 23.7 mg twice daily and at target trough concentrations of 10 –20 ng/mL, the dominant or effect-indicative half-life is estimated at...
Source: Clinical Pharmacokinetics - May 3, 2023 Category: Drugs & Pharmacology Source Type: research
Clinical Pharmacokinetics and Pharmacodynamics of Daratumumab
AbstractDaratumumab is a fully human, monoclonal immunoglobulin G1 and a first-in-class CD38-targeting drug approved by the US Food and Drug Administration for the treatment of patients with relapsed/refractory and newly diagnosed multiple myeloma or newly diagnosed light-chain amyloidosis. CD38 is heavily expressed on malignant myeloma cells, and daratumumab exerts anti-myeloma activity via immune-mediated mechanisms, direct induction of apoptosis, and immunomodulation. Daratumumab is used as monotherapy or in combination with standard-of-care myeloma therapies, including proteasome inhibitors, immunomodulatory agents, DN...
Source: Clinical Pharmacokinetics - May 2, 2023 Category: Drugs & Pharmacology Source Type: research
