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.

Machine Learning-led Optimization of Combination Therapy: Confronting the Public Health Threat of Extensively Drug Resistant Gram Negative Bacteria
This study utilized human population PK (PopPK) of aztreonam, ceftazidime/avibactam, and polymyxin B along with in vitro pharmacodynamics from the Hollow Fiber Infection Model (HFIM) to derive optimal multi-drug regimens de novo through implementation of a genetic algorithm (GA). The mechanism-based PD model was constructed based on 7-day HFIM experiments across four clinical, extensively drug resistant K. pneumoniae isolates. GA-led optimization was performed using thirteen different fitness functions to compare the effects of different efficacy (60%, 70%, 80% or 90% of simulated subjects achieving bacterial counts of 102...
Source: Clinical Pharmacology and Therapeutics - December 8, 2023 Category: Drugs & Pharmacology Authors: Nicholas M Smith Thomas D Nguyen Thomas P Lodise Liang Chen Jan Naseer Kaur John F Klem Katie Rose Boissonneault Patricia N Holden Dwayne R Roach Brian T Tsuji Source Type: research

Highlights
Clin Pharmacol Ther. 2023 Dec 8. doi: 10.1002/cpt.3122. Online ahead of print.NO ABSTRACTPMID:38063482 | DOI:10.1002/cpt.3122 (Source: Clinical Pharmacology and Therapeutics)
Source: Clinical Pharmacology and Therapeutics - December 8, 2023 Category: Drugs & Pharmacology Source Type: research

Risk of Toxicity from Topical 5-Fluorouracil Treatment in Patients Carrying DPYD Variant Alleles
The objective of this retrospective cohort study was to investigate whether DPYD variant allele carriers have increased risk of toxicity from topical 5-FU. Treatment and toxicity data were retrospectively abstracted from the electronic medical records. Genotypes for the five DPYD variants that are associated with increased toxicity from systemic fluoropyrimidine chemotherapy (DPYD*2A, DPYD*13, DPYD p.D949V, DPYD HapB3, and DPYD p.Y186C) were collected from a genetic data repository. Incidence of grade 3+ (primary endpoint) and 1+ (secondary endpoint) toxicity was compared between DPYD variant carriers vs. wild-type patient...
Source: Clinical Pharmacology and Therapeutics - December 7, 2023 Category: Drugs & Pharmacology Authors: Javier Granados Amy L Pasternak N Lynn Henry Vaibhav Sahai Daniel L Hertz Source Type: research

Characterisation of CYP2B6 and CYP2A6 pharmacogenetic variation in sub-Saharan African populations
This study therefore aimed to characterise the star allele (haplotype) distribution in CYP2B6 and CYP2A6 across diverse and understudied sub-Saharan African (SSA) populations. We called star alleles from 961 high-depth full genomes using StellarPGx, Aldy and PyPGx. In addition, we performed CYP2B6 and CYP2A6 star allele frequency comparisons between SSA and other global biogeographical groups represented in the new 1000 Genomes Project high-coverage dataset (n=2000). This study presents frequency information for star alleles in CYP2B6 (e.g. *6 and *18; frequency of 21-47% and 2-19%, respectively) and CYP2A6 (e.g. *4, *9 an...
Source: Clinical Pharmacology and Therapeutics - December 4, 2023 Category: Drugs & Pharmacology Authors: David Twesigomwe Britt I Dr ögemöller Galen E B Wright Clement Adebamowo Godfred Agongo Palwend é R Boua Mogomotsi Matshaba Maria Paximadis Mich èle Ramsay Gustave Simo Martin C Simuunza Caroline T Tiemessen Zan é Lombard Scott Hazelhurst Source Type: research