A better understanding of these unique differences may lead to expansion and/or improvement of GLP-1-based therapies for type 2 diabetes and obesity. Diabetes 58: 2820-2827, 2009″
“Many physiologic differences between children and adults can result in age-related differences in pharmacokinetics. Understanding
the effects of age oil bioavailability, volume of distribution, protein binding, hepatic metabolic isoenzymes, and renal elimination can provide insight into optimizing doses for pediatric patients. We performed a search of English-language literature using the MEDLINE database regarding age and pharmacokinetics (1979-July 2008). We then evaluated the literature with an emphasis on drugs with one primary elimination pathway, such as renal clearance or a pathway involving learn more a single metabolic isoenzyme. Our mechanistic-based analysis revealed that children need weight-corrected
doses that are substantially higher than adult doses for drugs that arc metabolically eliminated solely by the specific cytochrome P450 (CYP) isoenzymes CYP1A2, CYP2C9, and CYP3A4. In contrast, weight-corrected doses for drugs eliminated by renal excretion or metabolism involving CYP2C19, CYP2D6, N-acetyltransferase 2, or uridine diphosphate glucuronosyltransferases are similar in children and adults. In children, bioavailability of drugs with high first-pass metabolism is decreased for drugs metabolized by CYP1A2, CYP2C9, and CYP3A4. Limited data suggest that by age 5 years, bioavailability of drugs affected by efflux GW3965 cost transporters should be equivalent to that JQ1 ic50 of adults. Using a pharmacokinetics-based approach, rational predictions can be made for the effects of age on drugs that undergo similar pathways of elimination, even when specific pharmacokinetic data are limited or unavailable.”
“Mitochondrial dysfunction and mitochondria!
DNA (mtDNA) variations have been shown to have a role in several neurological diseases. To determine whether there is an association between mtDNA variations and spinocerebellar ataxia (SCA), we analyzed the mtDNA main control region (D-loop), as well as mtDNA content and the prevalence of the common deletion, in blood samples from members of a large Chinese family (14 individuals with SCA and 13 healthy individuals). All 14 individuals with SCA were genotyped as SCA3. Thirteen mtDNA haplotypes were identified among the 27 subjects. We detected no mutations in the mtDNA D-loop region and found no significant differences in mtDNA copy number or common deletion level between patients and their healthy relatives. Contrary to some previous reports, our study showed that mtDNA variations seem to be a rare event in individuals with SCA3. (C) 2011 Elsevier Ltd. All rights reserved.