The Journal of Clinical Pharmacology 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.

Single- and Multiple-Dose Pharmacokinetics of Gefapixant (MK-7264), a P2X3 Receptor Antagonist, in Healthy Adults
J Clin Pharmacol. 2024 Apr 23. doi: 10.1002/jcph.2442. Online ahead of print.ABSTRACTGefapixant (MK-7264, RO4926219, AF-219) is a first-in-class P2X3 antagonists being developed to treat refractory or unexplained chronic cough. The initial single- and multiple-dose safety, tolerability, and pharmacokinetics of gefapixant at doses ranging from 7.5 to 1800 mg were assessed in four clinical trials. Following single-dose administration of 10-450 mg, the pharmacokinetic (PK) profile of gefapixant in plasma and urine demonstrated low inter-subject variability and a dose-proportional exposure. Following administration of multiple...
Source: The Journal of Clinical Pharmacology - April 23, 2024 Category: Drugs & Pharmacology Authors: Jesse C Nussbaum Azher Hussain Peter Butera Anthony P Ford Michael M Kitt Edward A O'Neill Steven Smith Gabriel Vargas Terry O'Reilly Chris Wynne S Aubrey Stoch Marian Iwamoto Source Type: research

Characterizing the Nonlinear Pharmacokinetics and Pharmacodynamics of BI 187004, an 11 β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor, in Humans by a Target-Mediated Drug Disposition Model
This study aimed to construct a TMDD model to explain the complex nonlinear PK behavior and underscore the importance of recognizing TMDD in this small-molecule compound. Among the various models explored, the best model was a two-compartment TMDD model with three transit absorption components. The final model provides insights into 11β-HSD1 binding-related parameters for BI 187004, including the total amount of 11β-HSD1 in the liver (estimated to be 8000 nmol), the second order association rate constant (estimated to be 0.102 nM-1h-1), and the first-order dissociation rate constant (estimated to be 0.11 h-1). Our final ...
Source: The Journal of Clinical Pharmacology - April 23, 2024 Category: Drugs & Pharmacology Authors: Xuanzhen Yuan Guohua An Source Type: research

Effect of Hepatic Impairment on Trilaciclib Pharmacokinetics
J Clin Pharmacol. 2024 Apr 19. doi: 10.1002/jcph.2435. Online ahead of print.ABSTRACTTrilaciclib is a first-in-class, intravenous cyclin-dependent kinase 4 and 6 inhibitor approved for reducing the incidence of chemotherapy-induced myelosuppression in adult patients with extensive-stage small cell lung cancer receiving a platinum/etoposide-containing or topotecan-containing regimen. No dose adjustment is recommended for participants with mild hepatic impairment (HI) based on previous population pharmacokinetic (PK) analysis. This open-label, parallel-group study examined the impact of moderate and severe HI on the PK of tr...
Source: The Journal of Clinical Pharmacology - April 19, 2024 Category: Drugs & Pharmacology Authors: Chao Li Richard A Preston Emily Dumas Andrew Beelen Thomas C Marbury Source Type: research

Quantitative Assessment of Drug Efficacy and Emergence of Resistance in Patients with Metastatic Renal Cell Carcinoma Using a Longitudinal Exposure-Tumor Growth Inhibition Model: Apitolisib (Dual PI3K/mTORC1/2 Inhibitor) Versus Everolimus (mTORC1 Inhibitor)
J Clin Pharmacol. 2024 Apr 19. doi: 10.1002/jcph.2444. Online ahead of print.ABSTRACTCancer remains a significant global health challenge, and despite remarkable advancements in therapeutic strategies, poor tolerability of drugs (causing dose reduction/interruptions) and/or the emergence of drug resistance are major obstacles to successful treatment outcomes. Metastatic renal cell carcinoma (mRCC) accounts for 2% of global cancer diagnoses and deaths. Despite the initial success of targeted therapies in mRCC, challenges remain to overcome drug resistance that limits the long-term efficacy of these treatments. Our analysis ...
Source: The Journal of Clinical Pharmacology - April 19, 2024 Category: Drugs & Pharmacology Authors: Anita Moein Jin Y Jin Matthew R Wright Harvey Wong Source Type: research

Association of Vancomycin AUC/MIC and Trough Concentration With Early Clinical Response in Enterococcus or Coagulase-Negative Staphylococcus Infection: A Prospective Study
This study was condcuted to examine the association of area under the curve (AUC)/minimum inhibitory concentration (MIC) and trough concentration (Ctrough) of vancomycin with treatment outcome and nephrotoxicity in infections caused by Enterococcus spp. and coagulase-negative Staphylococci (CoNS). Peak and trough concentrations were used to calculate AUC in 89 patients receiving vancomycin for infections with Enterococcus spp. (n = 65) or CoNS (n = 24). Correlations between Ctrough, AUC/MIC, early clinical response (ECR), and nephrotoxicity were assessed and cutoff values were determined. Sixty-three (70.8%) patients showe...
Source: The Journal of Clinical Pharmacology - April 19, 2024 Category: Drugs & Pharmacology Authors: Chuleephorn Pitayakittiwong Pakawadee Sermsappasuk Atibordee Meesing Siriluk Jaisue Source Type: research

Population Pharmacokinetic Modeling and Exposure-Efficacy and Body Weight-Response Analyses for Tezepelumab in Patients With Severe, Uncontrolled Asthma
In conclusion, a fixed-dose regimen of tezepelumab 210 mg subcutaneously Q4W is appropriate for eligible adults and adolescents with severe, uncontrolled asthma.PMID:38632826 | DOI:10.1002/jcph.2433 (Source: The Journal of Clinical Pharmacology)
Source: The Journal of Clinical Pharmacology - April 18, 2024 Category: Drugs & Pharmacology Authors: Yanan Zheng Lubna Abuqayyas Angelica Quartino Ye Guan Yuying Gao Lu Liu Åsa Hellqvist Gene Colice Alexander MacDonald Source Type: research

Performance of ChatGPT on Factual Knowledge Questions Regarding Clinical Pharmacy
In this study, we examine its performance in answering factual knowledge questions regarding clinical pharmacy. Questions were obtained from a Dutch application that features multiple-choice questions to maintain a basic knowledge level for clinical pharmacists. In total, 264 clinical pharmacy-related questions were presented to ChatGPT and responses were evaluated for accuracy, concordance, quality of the substantiation, and reproducibility. Accuracy was defined as the correctness of the answer, and results were compared to the overall score by pharmacists over 2022. Responses were marked concordant if no contradictions w...
Source: The Journal of Clinical Pharmacology - April 16, 2024 Category: Drugs & Pharmacology Authors: Merel van Nuland Abdullah Erdogan Cenkay A ςar Ramon Contrucci Sven Hilbrants Lamyae Maanach Toine Egberts Paul D van der Linden Source Type: research

Assessment of CYP-Mediated Drug Interactions for Enasidenib Based on a Cocktail Study in Patients with Relapse or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
J Clin Pharmacol. 2024 Apr 2. doi: 10.1002/jcph.2436. Online ahead of print.ABSTRACTAs a selective and potent inhibitor targeting the isocitrate dehydrogenase-2 (IDH2) mutant protein, enasidenib obtained approval from the US Food and Drug Administration (FDA) in 2017 for adult patients with acute myeloid leukemia (AML) with an IDH2 mutation. In vitro investigations demonstrated that enasidenib affects various drug metabolic enzymes and transporters. This current investigation aimed to assess enasidenib on the pharmacokinetics (PKs) of CYP substrates, including dextromethorphan (CYP2D6 probe drug), flurbiprofen (CYP2C9 prob...
Source: The Journal of Clinical Pharmacology - April 2, 2024 Category: Drugs & Pharmacology Authors: Yiming Cheng Xiaomin Wang Atalanta Ghosh Jie Pu Leonidas N Carayannopoulos Yan Li Source Type: research