Clinical Pharmacology and Therapeutics This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

A Benefit-Risk Conceptual Framework for Biologic Use During Pregnancy: A Mini-Review
Clin Pharmacol Ther. 2024 Mar 20. doi: 10.1002/cpt.3239. Online ahead of print.ABSTRACTRecent reports related to in utero exposure of marketed immunosuppressive biologics led to clinical recommendations to delay live vaccinations for infants due to the concern of reduced vaccine effectiveness and/or increased risk of vaccine-related disease. These delays can increase the risk of children contracting vaccine preventable diseases, yet the alternative cessation of biologics during pregnancy may result in increased autoimmune disease activity for the pregnant person, raising complex benefit-risk (B-R) considerations and trade-...
Source: Clinical Pharmacology and Therapeutics - March 20, 2024 Category: Drugs & Pharmacology Authors: Laura M Bozzi Melanie H Jacobson Emily Yost Anna Sheahan Joseph Cafone Yosuke Komatsu Lisa Schwartz Bennett Levitan Robert M Nelson Source Type: research

Clinical Pharmacology Considerations for the "Off-the-Shelf" Allogeneic Cell Therapies
Clin Pharmacol Ther. 2024 Mar 19. doi: 10.1002/cpt.3241. Online ahead of print.ABSTRACTAutologous chimeric antigen receptor T-cell (CAR-T) therapies have garnered unprecedented clinical success with multiple regulatory approvals for the treatment of various hematological malignancies. However, there are still several clinical challenges that limit their broad utilization for aggressive disease conditions. To address some of these challenges, allogeneic cell therapies are evaluated as an alternative approach. As compared with autologous products, they offer several advantages, such as a more standardized "off the shelf" pro...
Source: Clinical Pharmacology and Therapeutics - March 19, 2024 Category: Drugs & Pharmacology Authors: Hardik Mody Dhruvitkumar S Sutaria Dale Miles Source Type: research

Predicting the Long-Term Effects of Therapeutic Neutralization of Oncostatin M on Human Hematopoiesis
Clin Pharmacol Ther. 2024 Mar 19. doi: 10.1002/cpt.3246. Online ahead of print.ABSTRACTTherapeutic neutralization of Oncostatin M (OSM) causes mechanism-driven anemia and thrombocytopenia, which narrows the therapeutic window complicating the selection of doses (and dosing intervals) that optimize efficacy and safety. We utilized clinical data from studies of an anti-OSM monoclonal antibody (GSK2330811) in healthy volunteers (n = 49) and systemic sclerosis patients (n = 35), to quantitatively determine the link between OSM and alterations in red blood cell (RBC) and platelet production. Longitudinal changes in hematopoieti...
Source: Clinical Pharmacology and Therapeutics - March 19, 2024 Category: Drugs & Pharmacology Authors: Anders Thorsted Chiara Zecchin Alienor Berges Mats O Karlsson Lena E Friberg Source Type: research

A Genome-Wide Association Study of Endoxifen Serum Concentrations and Adjuvant Tamoxifen Efficacy in Early-Stage Breast Cancer Patients
Clin Pharmacol Ther. 2024 Mar 19. doi: 10.1002/cpt.3255. Online ahead of print.ABSTRACTTamoxifen is part of the standard of care of endocrine therapy for adjuvant treatment of breast cancer. However, survival outcomes with tamoxifen are highly variable. The concentration of endoxifen, the 30-100 times more potent metabolite of tamoxifen and bioactivated by the CYP2D6 enzyme, has been described as the most relevant metabolite of tamoxifen metabolism. A genome-wide association study (GWAS) was performed with the objective to identify genetic polymorphisms associated with endoxifen serum concentration levels and clinical outc...
Source: Clinical Pharmacology and Therapeutics - March 19, 2024 Category: Drugs & Pharmacology Authors: Anabel Beatriz Sanchez-Spitman Stefan B öhringer Vincent Olaf Dezentj é Hans Gelderblom Jesse Joachim Swen Henk-Jan Guchelaar Source Type: research

Nonlinear Mixed-Effects Model of Z-Endoxifen Concentrations in Tamoxifen-Treated Patients from the CEPAM Cohort
Clin Pharmacol Ther. 2024 Mar 18. doi: 10.1002/cpt.3238. Online ahead of print.ABSTRACTTamoxifen is widely used in patients with hormone receptor-positive breast cancer. The polymorphic enzyme CYP2D6 is primarily responsible for metabolic activation of tamoxifen, resulting in substantial interindividual variability of plasma concentrations of its most important metabolite, Z-endoxifen. The Z-endoxifen concentration thresholds below which tamoxifen treatment is less efficacious have been proposed but not validated, and prospective trials of individualized tamoxifen treatment to achieve Z-endoxifen concentration thresholds a...
Source: Clinical Pharmacology and Therapeutics - March 18, 2024 Category: Drugs & Pharmacology Authors: Anna M Mc Laughlin Thomas Helland Fenja Klima Stijn L W Koolen Ron H N van Schaik Ron H J Mathijssen Patrick Neven Jesse J Swen Henk-Jan Guchelaar Florence Dalenc Melanie White-Koning Robin Michelet Gerd Mikus Werner Schroth Thomas M ürdter Hiltrud Brauc Source Type: research

A Case to Support the Continued Use of Rifampin in Clinical Drug-Drug Interaction Studies
Clin Pharmacol Ther. 2024 Mar 18. doi: 10.1002/cpt.3256. Online ahead of print.NO ABSTRACTPMID:38494918 | DOI:10.1002/cpt.3256 (Source: Clinical Pharmacology and Therapeutics)
Source: Clinical Pharmacology and Therapeutics - March 18, 2024 Category: Drugs & Pharmacology Authors: Joel P Bercu David J Ponting Sharon L Ripp Krista L Dobo Rheem A Totah Jayaprakasam Bolleddula Source Type: research

Assessment of Dosing Strategies for Pediatric Drug Products
Clin Pharmacol Ther. 2024 Mar 17. doi: 10.1002/cpt.3250. Online ahead of print.ABSTRACTPediatric drug dosing is challenged by the heterogeneity of developing physiology and ethical considerations surrounding a vulnerable population. Often, pediatric drug dosing leverages findings from the adult population; however, recent regulatory efforts have motivated drug sponsors to pursue pediatric-specific programs to meet an unmet medical need and improve pediatric drug labeling. This paradigm is further complicated by the pathophysiological implications of obesity on drug distribution and metabolism and the roles that body compos...
Source: Clinical Pharmacology and Therapeutics - March 17, 2024 Category: Drugs & Pharmacology Authors: Zachary L Taylor Francis G Green Nayeem Hossain Gilbert J Burckart Michael Pacanowski Robert N Schuck Source Type: research

Genome-Wide Association Study of Atorvastatin Pharmacokinetics: Associations With SLCO1B1, UGT1A3, and LPP
Clin Pharmacol Ther. 2024 Mar 17. doi: 10.1002/cpt.3236. Online ahead of print.ABSTRACTIn a genome-wide association study of atorvastatin pharmacokinetics in 158 healthy volunteers, the SLCO1B1 c.521T>C (rs4149056) variant associated with increased area under the plasma concentration-time curve from time zero to infinity (AUC0-∞ ) of atorvastatin (P = 1.2 × 10-10 ), 2-hydroxy atorvastatin (P = 4.0 × 10-8 ), and 4-hydroxy atorvastatin (P = 2.9 × 10-8 ). An intronic LPP variant, rs1975991, associated with reduced atorvastatin lactone AUC0-∞ (P = 3.8 × 10-8 ). Three UGT1A variants linked with UGT1A3*2 associated wi...
Source: Clinical Pharmacology and Therapeutics - March 17, 2024 Category: Drugs & Pharmacology Authors: Anssi J H Mykk änen E Katriina Tarkiainen Suvi Taskinen Mikko Neuvonen Maria Paile-Hyv ärinen Tuomas O Lilius Tuija Tapaninen Kathrin Klein Matthias Schwab Janne T Backman Aleksi Tornio Mikko Niemi Source Type: research

Combination Therapy With Guselkumab and Golimumab in Patients With Moderately to Severely Active Ulcerative Colitis: Pharmacokinetics, Immunogenicity and Drug-Drug Interactions
Clin Pharmacol Ther. 2024 Mar 15. doi: 10.1002/cpt.3235. Online ahead of print.ABSTRACTA proof-of-concept study with the combination of guselkumab and golimumab in patients with ulcerative colitis (UC) has shown that the combination therapy resulted in greater efficacy than the individual monotherapies. The current analysis evaluated the pharmacokinetics (PK) and immunogenicity of guselkumab and golimumab in both the combination therapy and individual monotherapies. Blood samples were collected to evaluate serum concentrations and immunogenicity of guselkumab and golimumab. Population PK (PopPK) models were developed to as...
Source: Clinical Pharmacology and Therapeutics - March 15, 2024 Category: Drugs & Pharmacology Authors: Jie Shao Marion Vetter An Vermeulen Brian G Feagan Bruce E Sands Julian Pan és Zhenhua Xu Source Type: research

Comparative Risk of Injury with Concurrent Use of Opioids and Skeletal Muscle Relaxants
In conclusion, the relative injury rate associated with different SMRs used concurrently with the three most dispensed opioids appears to vary depending on the specific opioid and the order of combination initiation. If confirmed by future studies, clinicians should consider the varying injury rates when prescribing SMRs to individuals using hydrocodone, oxycodone, and tramadol.PMID:38482733 | DOI:10.1002/cpt.3248 (Source: Clinical Pharmacology and Therapeutics)
Source: Clinical Pharmacology and Therapeutics - March 14, 2024 Category: Drugs & Pharmacology Authors: Cheng Chen Sean Hennessy Colleen M Brensinger Todd A Miano Warren B Bilker Sascha Dublin Sophie P Chung John R Horn Anika Tiwari Charles E Leonard Source Type: research

Gene Polymorphisms of NLRP3 Associated With Plasma Levels of 4 β-Hydroxycholesterol, an Endogenous Marker of CYP3A Activity, in Patients With Asthma
Clin Pharmacol Ther. 2024 Mar 14. doi: 10.1002/cpt.3254. Online ahead of print.ABSTRACTInflammation decreases the activity of cytochrome P450 3A (CYP3A). Nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) is responsible for regulating the inflammatory response, and its genetic polymorphisms have been linked to inflammatory diseases such as asthma. However, there have been few studies on the effect of NLRP3 on CYP3A activity. We aimed to investigate the association between polymorphisms in the NLRP3 gene and plasma 4β-hydroxycholesterol (4βOHC), an endogenous marker of C...
Source: Clinical Pharmacology and Therapeutics - March 14, 2024 Category: Drugs & Pharmacology Authors: Keita Hirai Tomoki Kimura Yuya Suzuki Takayuki Shimoshikiryo Toshihiro Shirai Kunihiko Itoh Source Type: research