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- Haslemo, T, et al.
(författare)
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UGT1A4*3 encodes significantly increased glucuronidation of olanzapine in patients on maintenance treatment and in recombinant systems
- 2012
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Ingår i: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 92:2, s. 221-227
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Tidskriftsartikel (refereegranskat)abstract
- Olanzapine, a world leader in antipsychotic drugs, is used in the treatment of schizophrenia and bipolar disorder. There is considerable interpatient variability in its hepatic clearance. Polymorphic glucuronidation of olanzapine by uridine diphosphate glucuronosyltransferase 1A4 (UGT1A4) was investigated retrospectively in patient samples taken for routine therapeutic drug monitoring (TDM) and in recombinant metabolic systems in vitro. Multivariate analyses revealed that patients who were heterozygous as well as those who were homozygous for the UGT1A4*3 allelic variant had significantly higher concentrations of the major metabolite olanzapine 10-N-glucuronide in serum (+38% (P = 0.011) and +246% (P < 0.001), respectively). This finding was in line with the significant increases in glucuronidation activity of olanzapine observed with recombinant UGT1A4.3 (Val-48) as compared with UGT1A4.1 (Leu-48) (1.3-fold difference, P < 0.001). By contrast, serum concentrations of the parent drug were not significantly influenced by UGT1A4 genotype. Our findings therefore indicate that UGT1A4-mediated metabolism is not a major contributor to interpatient variability in olanzapine levels. However, with respect to other drugs for which UGT1A4 has a dominant role in clearance, increased glucuronidation encoded by UGT1A4*3 might impact the risk for subtherapeutic drug exposure.
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| 3. |
- Boelee, Eline, et al.
(författare)
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Management of Water and Agroecosystems in Landscapes for Sustainable Food Security
- 2013
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Ingår i: Managing water and agroecosystems for food security. - Wallingford : CABI Publishing. - 9781780640884 ; , s. 156-170
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Bokkapitel (refereegranskat)abstract
- Various food and financial crises have increased the pressure on natural resources while expanding on alternative ways of considering agroecosystems as potential long-term providers of ecosystem services if managed in a sustainable and equitable way. Through the study of interrelations between ecosystems, water and food security, this book has aimed to increase the understanding and knowledge of these interactions for better planning and decision making processes at various levels. This chapter concludes Managing Water and Agroecosystems for Food Security. It discusses the main findings of the preceding chapters, from analyses of drivers of sustainable food security, via agroecosystems with their ecosystem services and challenges for water use and scarcity, to specific challenges for environments such as drylands and wetlands. Using a comprehensive landscape approach, recommendations on water productivity, agroecosystem services and integrated water management are brought together succinctly. In addition, knowledge gaps and issues for further research have been identified that may support further implementation of the agroecological approach in many landscapes around the world.
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