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Quantitation and characterization of glucosylsphingosine in cerebrospinal fluid (CSF), plasma, and brain of monkey model with Gaucher disease
Drug Metab Pharmacokinet. 2023 Sep 15;53:100530. doi: 10.1016/j.dmpk.2023.100530. Online ahead of print.ABSTRACTTreatment with conduritol-β-epoxide (CBE) in preclinical species is expected to be a powerful approach to generate animal models of Gaucher disease (GD) and Parkinson's disease associated with heterozygous mutations in Glucocerebrosidase (GBA-PD). However, it is not fully elucidated how quantitatively the change in glucosylsphingosine (GlcSph) levels in cerebrospinal fluid (CSF) correlates with that in the brain, which is expected to be clinically informative. Herein, we aimed to investigate the correlation with...
Source: Drug Metabolism and Pharmacokinetics - November 4, 2023 Category: Drugs & Pharmacology Authors: Sho Sato Shin-Ichi Matsumoto Yohei Kosugi Source Type: research

A model-based pharmacokinetic assessment of drug-drug interaction between tacrolimus and nirmatrelvir/ritonavir in a kidney transplant patient with COVID-19
In conclusion, nirmatrelvir/ritonavir greatly increases tacrolimus concentrations by not only reducing clearance, but also increasing bioavailability. Interactions between nirmatrelvir/ritonavir and low-bioavailability drugs which are substrates for CYP3A and P-glycoprotein, such as tacrolimus, are harmful, and concomitant use of these medicines should be avoided.PMID:37924724 | DOI:10.1016/j.dmpk.2023.100529 (Source: Drug Metabolism and Pharmacokinetics)
Source: Drug Metabolism and Pharmacokinetics - November 4, 2023 Category: Drugs & Pharmacology Authors: Takeshi Tomida Kotaro Itohara Kazuhiro Yamamoto Takeshi Kimura Kohei Fujita Atsushi Uda Yumi Kitahiro Naoki Yokoyama Yoji Hyodo Tomohiro Omura Ikuko Yano Source Type: research

Analysis of the interplay of physiological response to food intake and drug properties in food-drug interactions
This study aimed to identify key drug properties that influence food effect (FE) using supervised machine learning approaches. The analysis showed that drugs with high logP, dose number, and extraction ratio have a higher probability of positive FE, while drugs with low permeability and high efflux saturation index have a greater likelihood of negative FE. Weakly acidic drugs also showed a greater probability of positive FE, particularly at pKa >4.3. The importance of drug properties in predicting FE was ranked as logP, dose number, extraction ratio, pKa, and permeability. The accuracy of FE prediction using the models ...
Source: Drug Metabolism and Pharmacokinetics - October 19, 2023 Category: Drugs & Pharmacology Authors: Sheena Sharma Clark Kogan Manthena V S Varma Bhagwat Prasad Source Type: research

Simple confirmation methods for rare but impaired variants of human flavin-containing monooxygenase 3 (FMO3) found in an updated genome resource databank
Drug Metab Pharmacokinet. 2023 Aug 23;53:100528. doi: 10.1016/j.dmpk.2023.100528. Online ahead of print.ABSTRACTForty-seven new nonsense or missense human flavin-containing monooxygenase 3 (FMO3) variants were recently identified in an updated Japanese population reference panel. Of these, 20 rare single-nucleotide substitutions resulted in moderately or severely impaired FMO3 activity. To easily identify these 20 FMO3 variants (2 stop codon mutations, 2 frameshifts, and 16 amino-acid substitutions) in the clinical setting, simple confirmation methods for impaired FMO3 variants are proposed using polymerase chain reaction ...
Source: Drug Metabolism and Pharmacokinetics - October 19, 2023 Category: Drugs & Pharmacology Authors: Makiko Shimizu Miaki Makiguchi Yuka Yokota Erika Shimamura Moegi Matsuta Yuria Nakamura Mizuki Harano Hiroshi Yamazaki Source Type: research