Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of some hypolipidemic agents, which are commercially available and those being developed, on certain biochemical values and on hepatic peroxisomal enzyme activities of rats were examined. Clofibrate (0.25% (w/w) in the diet), p-chlorophenoxy-isobutyryl-glycinamide (CGA) (0.25%), clinofibrate (0.1%), KCD-232 (0.1%) and MLM-160 (0.1%) increased the activities of peroxisomal fatty acyl-CoA oxidizing system, carnitine acetyltransferase, and mitochondrial carnitine palmitoyltransferase. Of peroxisomal enzymes, catalase activity was increased by the above agents, whereas the activities of D-amino acid oxidase and urate oxidase were decreased by clofibrate and CGA, and but were increased by KCD-232 and MLM-160 which are structurally unrelated to clofibrate. No influence on these enzyme activities by AL-369 and probucol treatments were observed. Hepatomegaly was induced by clofibrate, CGA, KCD-232 and MLM-160. Concerning serum lipid levels, clofibrate, CGA, clinofibrate, KCD-232 and MLM-160 decreased both cholesterol and triglyceride levels, whereas probucol decreased only cholesterol level. AL-369 had no influence on serum lipid levels under this condition using normolipemic rat. From these results, it was concluded that differing clofibrate and CGA, clinofibrate, MLM-160 and KCD-232 might not induce peroxisome proliferation in hepatic cells, although these have an influence on the enzyme composition of hepatic peroxisomes.
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PMID:Effects of some hypolipidemic agents on biochemical values and hepatic peroxisomal enzymes in rats: comparison of probucol, CGA, KCD-232, MLM-160, AL-369 and clinofibrate with clofibrate. 362 48

The goal of this study was to explore the relationships between tenofovir (TFV) and emtricitabine (FTC) disposition and markers of biologic aging, such as the frailty phenotype and p16INK4a gene expression. Chronologic age is often explored in population pharmacokinetic (PK) analyses, and can be uninformative in capturing the impact of aging on physiology, particularly in human immunodeficiency virus (HIV)-infected patients. Ninety-one HIV-infected participants provided samples to quantify plasma concentrations of TFV/FTC, as well as peripheral blood mononuclear cell (PBMC) samples for intracellular metabolite concentrations; 12 participants provided 11 samples, and 79 participants provided 4 samples, over a dosing interval. Nonlinear mixed effects modeling of TFV/FTC and their metabolites suggests a relationship between TFV/FTC metabolite clearance (CL) from PBMCs and the expression of p16INK4a , a marker of cellular senescence. This novel approach to quantifying the influence of aging on PKs provides rationale for further work investigating the relationships between senescence and nucleoside phosphorylation and transport.
CPT Pharmacometrics Syst Pharmacol 2017 02
PMID:p16INK4a , a Senescence Marker, Influences Tenofovir/Emtricitabine Metabolite Disposition in HIV-Infected Subjects. 2801 88

Unbound drug is the pharmacodynamically relevant concentration. This study aimed to determine if chronologic age or markers of biologic aging, such as the frailty phenotype and p16INK4a gene expression, altered unbound pharmacokinetics (PKs) of efavirenz (EFV) and atazanavir/ritonavir (ATV/RTV). Sixty human immunodeficiency virus (HIV)-infected participants receiving EFV and 31 receiving ATV/RTV provided 1 to 11 samples to quantify total and unbound plasma concentrations. Population PK models with total and unbound concentrations simultaneously described are developed for each drug. The unbound fractions for EFV, ATV, and RTV are 0.65%, 5.67%, and 0.63%, respectively. Covariate analysis suggests RTV unbound PK is sensitive to body size; unbound fraction of RTV is 34% lower with body mass index (BMI) above 30 kg/m2 . No alterations in drug clearance or unbound fraction with age, frailty, or p16INK4a expression were observed. Assessing functional and physiologic aging markers to inform potential PK changes is necessary to determine if drug/dosing changes are warranted in the aging population.
CPT Pharmacometrics Syst Pharmacol 2017 02
PMID:Population Pharmacokinetics Modeling of Unbound Efavirenz, Atazanavir, and Ritonavir in HIV-Infected Subjects With Aging Biomarkers. 2803 46