Population Target-Mediated Pharmacokinetic/Pharmacodynamic Modeling to Evaluate SPI-62 Exposure and Hepatic 11 β-Hydroxysteroid Dehydrogenase Type 1 (HSD-1) Inhibition in Healthy Adults
ConclusionsA population TMDD-PD model that explains SPI-62 nonlinear PK and hepatic HSD-1 inhibition following different dose regimens in healthy adults was successfully established. Our simulation results provide a solid foundation for model-informed development of SPI-62. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - July 15, 2023 Category: Drugs & Pharmacology Source Type: research
Relationship Between Cetuximab Target-Mediated Pharmacokinetics and Progression-Free Survival in Metastatic Colorectal Cancer Patients
ConclusionThis is the first study describing the complex relationship between cetuximab target-mediated pharmacokinetics and PFS in mCRC patients using a joint PK-time-to-progression model. Further studies are needed to provide a more in-depth description of this relationship. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - July 13, 2023 Category: Drugs & Pharmacology Source Type: research
Population Pharmacokinetic Model of Intravenous Busulfan in Hematopoietic Cell Transplantation: Systematic Review and Comparative Simulations
ConclusionBusulfan PK is commonly described using a first-order elimination or time-varying CL. A simple model with limited covariates were generally sufficient to attain relatively small unexplained variabilities. However, therapeutic drug monitoring may still be necessary to attain a narrow target exposure. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - July 6, 2023 Category: Drugs & Pharmacology Source Type: research
Unraveling Complexities in the Absorption and Disposition Kinetics of Abiraterone via Iterative PBPK Model Development and Refinement
ConclusionOur systematic development of the abiraterone PBPK model has demonstrated its application for the prospective interrogation of the individual or combined influences of potential interindividual variabilities influencing the systemic exposure of abiraterone. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - July 5, 2023 Category: Drugs & Pharmacology Source Type: research
Pharmacokinetics of Nasal Esketamine in Patients with Allergic Rhinitis with and Without Nasal Decongestant Pretreatment and in Healthy Subjects with and Without Nasal Corticosteroid Pretreatment
ConclusionsPatients exhibiting symptoms of rhinitis may receive nasal esketamine spray without dose adjustment. In addition, esketamine may be administered 1 h after using a nasal decongestant or corticosteroid.Trial RegistrationThe study was registered in the Clinical Trials (NCT02154334) and EudraCT (2014 ‐000534‐38) registries. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - July 4, 2023 Category: Drugs & Pharmacology Source Type: research
Pharmacokinetics, Metabolism, and Excretion of Intravenous [14C]Difelikefalin in Healthy Subjects and Subjects on Hemodialysis
ConclusionIn subjects on HD, difelikefalin total exposure was higher and plasma half-life was longer compared with subjects with intact renal function. Metabolism was low in both healthy subjects and subjects on HD, with unchanged drug representing> 99% of systemic circulation; however, the route of excretion was primarily into urine versus feces in healthy subjects, and feces versus dialysate in subjects on HD.RegistrationClinicalTrials.gov NCT03947970. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - June 28, 2023 Category: Drugs & Pharmacology Source Type: research
Correction to: Effect of Various Dosing Schedules on the Pharmacokinetics of Oral Semaglutide: A Randomised Trial in Healthy Subjects
(Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - June 28, 2023 Category: Drugs & Pharmacology Source Type: research
Pharmacokinetics, Metabolism, and Excretion of Intravenous [14C]Difelikefalin in Healthy Subjects and Subjects on Hemodialysis
ConclusionIn subjects on HD, difelikefalin total exposure was higher and plasma half-life was longer compared with subjects with intact renal function. Metabolism was low in both healthy subjects and subjects on HD, with unchanged drug representing> 99% of systemic circulation; however, the route of excretion was primarily into urine versus feces in healthy subjects, and feces versus dialysate in subjects on HD.RegistrationClinicalTrials.gov NCT03947970. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - June 28, 2023 Category: Drugs & Pharmacology Source Type: research
Correction to: Effect of Various Dosing Schedules on the Pharmacokinetics of Oral Semaglutide: A Randomised Trial in Healthy Subjects
(Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - June 28, 2023 Category: Drugs & Pharmacology Source Type: research
A Randomized Open-Label Study of Relugolix Alone or Relugolix Combination Therapy in Premenopausal Women
ConclusionsRelugolix 40 mg in combination with E2 1 mg and NETA 0.5 mg provided systemic E2 concentrations within a range expected to minimize the risk of undesirable effects of hypoestrogenism associated with the administration of relugolix alone.Clinical Trial RegistrationClinicaltrials.gov identifier no. NCT04978688. Trial registration date: 27 July, 2021; retrospectively registered. (Source: Clinical Pharmacokinetics)
Source: Clinical Pharmacokinetics - June 26, 2023 Category: Drugs & Pharmacology Source Type: research
