Plasma efavirenz concentrations and the association with CYP2B6-516G >T polymorphism in HIV-infected Thai children.
作者： Tim R Cressey , Linda Aurpibul , Pranoot Tanpaiboon , Thanyawee Puthanakit , Virat Sirisanthana
DOI:
关键词:
摘要: Background Concerns have been raised about the possibility of subtherapeutic efavirenz (EFV) plasma levels in children with current dosing guideline. Single nucleotide polymorphisms hepatic cytochrome P450 isoenzyme 2B6 (CYP2B6) gene associated high interindividual variations EFV concentrations. Our objective was to determine adequacy and explore influence CYP2B6-516G>T on concentrations Thai HIV-infected children. Methods A total 63 receiving for > or =4 weeks were assessed. Children received daily doses basis body weight bands. Between 12 16 h after intake, a blood sample drawn measure concentration polymorphism using HPLC direct sequencing, respectively. Results The median age (range) 12.3 years (3.1-18.7). mean (+/-sd) 3,138 ng/ml (3,313). Eight (13%), 45 (71%) 10 (16%) had an 4,000 ng/ml, CYP2B6-516 G/G, G/T T/T genotypes found 48%, 41% 11% children, allele frequency 31.75%. 1,604 (729), 2,635 (1,199) 11,582 (2,972), respectively (P psychiatric side effects observed (P=0.02), but there no association rash, hepatotoxicity central nervous system disturbances. Conclusions Current guidelines provide adequate drug significantly affect metabolism
参考文章(26)
Magnus Ingelman-Sundberg, Stefan Lundgren, Filip Josephson, Lars Ståhle, Anders Sönnerborg, Jue Wang, Anders Rane, Identification of a novel specific CYP2B6 allele in Africans causing impaired metabolism of the HIV drug efavirenz. Pharmacogenetics and Genomics. ,vol. 16, pp. 191- 198 ,(2006) , 10.1097/01.FPC.0000189797.03845.90
Heather J Ribaudo, Catia Marzolini, Todd Hulgan, David B Clifford, Richard B Kim, Edward P Acosta, Roy M Gulick, David W Haas, Camlin Tierney, Grant R Wilkinson, Pharmacogenetics of efavirenz and central nervous system side effects: an Adult AIDS Clinical Trials Group study. AIDS. ,vol. 18, pp. 2391- 2400 ,(2004)
Thomas Lang, Kathrin Klein, Joachim Fischer, Andreas Nussler, Peter Neuhaus, Ute Hofmann, Michel Eichelbaum, Matthias Schwab, Ulrich Zanger, Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Pharmacogenetics. ,vol. 11, pp. 399- 415 ,(2001) , 10.1097/00008571-200107000-00004
Thomas Lang, Tanja Saussele, Eduardo Barbosa-Sicard, Wolf-Hagen Schunck, Michel Eichelbaum, Matthias Schwab, Ulrich M. Zanger, Kathrin Klein, Genetic variability of CYP2B6 in populations of African and Asian origin: allele frequencies, novel functional variants, and possible implications for anti-HIV therapy with efavirenz. Pharmacogenetics and Genomics. ,vol. 15, pp. 861- 873 ,(2005) , 10.1097/01213011-200512000-00004
Su Guan, Min Huang, Eli Chan, Xiao Chen, Wei Duan, Shu-Feng Zhou, Genetic polymorphisms of cytochrome P450 2B6 gene in Han Chinese European Journal of Pharmaceutical Sciences. ,vol. 29, pp. 14- 21 ,(2006) , 10.1016/J.EJPS.2006.04.004
Akihiko Saitoh, Kumud K Singh, Christine A Powell, Terrence Fenton, Courtney V Fletcher, Richard Brundage, Stuart Starr, Stephen A Spector, An MDR1-3435 variant is associated with higher plasma nelfinavir levels and more rapid virologic response in HIV-1 infected children. AIDS. ,vol. 19, pp. 371- 380 ,(2005) , 10.1097/01.AIDS.0000161766.13782.2F
Dorie W. Hoody, Courtney V. Fletcher, Pharmacology considerations for antiretroviral therapy in human immunodeficiency virus (HIV)-infected children. Seminars in Pediatric Infectious Diseases. ,vol. 14, pp. 286- 294 ,(2003) , 10.1053/J.SPID.2003.09.004
Shigeru Yamano, Patson T. Nhamburo, Toshifumi Aoyama, Urs A. Meyer, Tadanobu Inaba, Werner Kalow, Harry V. Gelboin, O. Wesley McBride, Frank J. Gonzalez, cDNA cloning and sequence and cDNA-directed expression of human P450 IIB1: identification of a normal and two variant cDNAs derived from the CYP2B locus on chromosome 19 and differential expression of the IIB mRNAs in human liver. Biochemistry. ,vol. 28, pp. 7340- 7348 ,(1989) , 10.1021/BI00444A029
R. E. McKinney, J. Rodman, C. Hu, P. Britto, M. Hughes, M. E. Smith, L. K. Serchuck, J. Kraimer, A. A. Ortiz, P. Flynn, R. Yogev, S. Spector, L. Draper, P. Tran, M. Scites, R. Dickover, A. Weinberg, C. Cunningham, E. Abrams, M. R. Blum, G. E. Chittick, L. Reynolds, M. Rathore, , Long-term safety and efficacy of a once-daily regimen of emtricitabine, didanosine, and efavirenz in HIV-infected, therapy-naive children and adolescents: Pediatric AIDS Clinical Trials Group Protocol P1021. Pediatrics. ,vol. 120, ,(2007) , 10.1542/PEDS.2006-0925
Yuan Ren, James J C Nuttall, Claire Egbers, Brian S Eley, Tammy M Meyers, Peter J Smith, Gary Maartens, Helen M McIlleron, High Prevalence of Subtherapeutic Plasma Concentrations of Efavirenz in Children Journal of Acquired Immune Deficiency Syndromes. ,vol. 45, pp. 133- 136 ,(2007) , 10.1097/QAI.0B013E31805C9D52