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Abstrak-Polymorphism-Of-PXR-Gene Review Articles Free Access Management of opioid-induced constipation in pregnancy: a concise review with emphasis on the PAMORAs Z. Li PharmD J. V. Pergolizzi MD R. P. Huttner MD G. Zampogna MD F. Breve PharmD R. B. Raffa PhD Pages: 615-619 First Published: 17 November 2015 Kawasaki disease: a comprehensive review of treatment options Rupal M. Patel PharmD Stanford T. Shulman MD Pages: 620-625 First Published: 07 November 2015 Hyponatraemia induced by terlipressin: a case report and literature review Y. Huang MD M. Wang MM J. Wang MD Pages: 626-628 First Published: 17 November 2015 The role of abuse-deterrent formulations in countering opioid misuse and abuse V. Nguyen PharmD R. B. Raffa PhD R. Taylor PhD J. V. Pergolizzi MD Jr Pages: 629-634 First Published: 23 November 2015 Original Articles Evaluation of initial dofetilide dosing recommendation based on actual body weight in overweight and obese patients D. X. Cao PharmD A. Kohatsu PharmD L. Eng PharmD K. Mei PharmD J. Dinh PharmD I. Mok PharmD N. Moreau PharmD A. Le PharmD J. Shin PharmD Pages: 635-639 First Published: 14 September 2015 Vancomycin serum trough concentration vs. clinical outcome in patients with gram-positive infection: a retrospective analysis G. Cao MSc X. Liang MMSc J. Zhang PhD Y. Zhou MD, PhD J. Wu Bmed Y. Zhang Bmed Y. Chen PhD J. Huang MSc X. Liu MSc J. Yu BSc Pages: 640-644 First Published: 18 September 2015 Medication safety at the interface: evaluating risks associated with discharge prescriptions from mental health hospitals R. N. Keers MPharm PGDip PhD S. D. Williams BPharm ClinDipPharm IPresc MPhil J. J. Vattakatuchery MD MRCPsych P. Brown BPharm J. Miller BPharm L. Prescott BPharm D. M. Ashcroft BPharm MSc PhD Pages: 645-654 First Published: 03 November 2015 Evaluation of a Clostridium difficile infection management policy with clinical pharmacy and medical microbiology involvement at a major Canadian teaching hospital S. S. T. Yeung BSc, (Pharm), ACPR, MSc J. K. Yeung BSc, (Pharm), ACPR, Pharm D T. T. Y. Lau Pharm D, ACPR, FCSHP L. A. Forrester MA, MSc T. S. Steiner MD W. R. Bowie MD, FRCPC E. A. Bryce MD, FRCPC Pages: 655-660 First Published: 07 November 2015 Effect of smoking status on progression-free and overall survival in non-small cell lung cancer patients receiving erlotinib or gefitinib: a meta-analysis H. S. Sohn PhD J.-W. Kwon PhD S. Shin PharmD H.-S. Kim MD, PhD H. Kim PharmD BCPS Pages: 661-671 First Published: 17 November 2015 Pharmacogenetics The impact of CYP2C19 polymorphisms on citalopram metabolism in patients with major depressive disorder Z. Uckun PhD B. Baskak MD E. T. Ozel-Kizil MD H. Ozdemir MD H. Devrimci Ozguven MD H. S. Suzen PhD Pages: 672-679 First Published: 07 September 2015 Polymorphism of PXR gene associated with the increased risk of drug-induced liver injury in Indonesian pulmonary tuberculosis patients Z. Zazuli MPharm M. I. Barliana PhD U. A. Mulyani MSc D. A. Perwitasari PhD H. Ng BPharm R. Abdulah PhD Pages: 680-684 First Published: 29 September 2015 The influence of ABCB1 polymorphism C3435T on the pharmacokinetics of silibinin Z. R. Tan PhD Y. X. Zhou MD J. Liu MD W. H. Huang PhD Y. Chen PhD Y. C. Wang MD L. S. Wang PhD Pages: 685-688 First Published: 23 November 2015 Case Reports Febuxostat-associated drug reaction with eosinophilia and systemic symptoms (DRESS) H.-Y. Chou MS C.-B. Chen MD C.-Y. Cheng MS Y.-A. Chen MS C. Y. Ng MD K.-L. Kuo MD W.-L. Chen MS C.-H. Chen MS Pages: 689-692 First Published: 14 September 2015 Probable interaction between acenocoumarol and levofloxacin: a case series I. Palacios-Zabalza PharmD M. Bustos-Martínez BScPharm J. Peral-Aguirregoitia PharmD M. J. Martínez-Bengoechea PharmD C. Aguirre Gomez MD Pages: 693-695 First Published: 23 September 2015 False-negative cerebrospinal fluid fungal culture results following oral antineoplastic therapy with a 5-fluorouracil derivative W. R. Judd PharmD, BCPS R. N. Shely PharmD, BCPS P. D. Ratliff PharmD, BCPS M. T. Reymann MD Pages: 696-698 First Published: 12 October 2015 Zolpidem test and catatonia H. Javelot PharmD, PhD B. Michel PharmD, PhD R. Steiner MD T. Javelot MD O. Cottencin MD, PhD Pages: 699-701 First Published: 07 November 2015 Prolonged use of fondaparinux for perioperative bridging: a case report of a patient with mechanical heart valve and heparin-induced thrombocytopenia M. Wei PharmaD C. T. Wang MD D. M. Li MD X. J. Song PharmaD Pages: 702-705 First Published: 17 November 2015 Journal of Clinical Pharmacy and Therapeutics, 2015, 40,680–684 doi: 10.1111/jcpt.12325 Pharmacogenetics Polymorphism of PXR gene associated with the increased risk of drug-induced liver injury in Indonesian pulmonary tuberculosis patients Z. Zazuli* MPharm, M. I. Barliana† PhD, U. A. Mulyani‡ MSc, D. A. Perwitasari§ PhD, H. Ng* BPharm and R. Abdulah* PhD *Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, †Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, ‡Center for Applied Health Technology and Clinical Epidemiology, National Institute of Health Research and Development, Ministry of Health Republic of Indonesia, Jakarta, and §Faculty of Pharmacy, Universitas Ahmad Dahlan, Yogyakarta, Indonesia Received 25 December 2014, Accepted 25 August 2015 Keywords: antituberculosis drugs, drug-induced hepatotoxicity, drug-induced liver injury, polymorphism, PXR positive). The corresponding figures for Indonesia are 325 582, and SUMMARY 7964 cases of TB have been identified as new and relapse cases, What is known and objective: Tuberculosis is still a major respectively.1 Given this high burden of disease, the government of infectious disease in Indonesia. Patients are treated mostly using Indonesia is focusing on the control and elimination of TB. One of fixed-dose combination treatment in primary public health the efforts is through the directly observed treatment, short-course facilities. The incidence of antituberculosis drug-induced liver strategy (DOTS) programme. injury (AT-DILI) is approximately 10% among Indonesian One of the main concerns in antituberculosis drugs (ATDs) is tuberculosis patients who used standard fixed combination drug-induced liver injury (DILI) or hepatotoxicity caused by regimens during the intensive phase of treatment. However, drugs.2 Of the first-line anti-TB drugs, isoniazid, pyrazinamide information regarding genetic polymorphism associated with and rifampicin can all cause liver damage (drug-induced hepati- the increase risk of drug-induced liver injury is still limited. The tis).3 In addition, rifampicin can cause asymptomatic jaundice aim of this study was to investigate pregnane X receptor (PXR) without evidence of hepatitis.3 A previous publication has shown gene polymorphisms as one of the risk factors of AT-DILI. that the incidence of antituberculosis drug-induced liver injury Methods: In this prospective cohort study, we recruited 106 adult (AT-DILI) is around 10% among Indonesian TB patients treated patients diagnosed with pulmonary tuberculosis and treated with standard fixed combination regimens during the intensive with category I FDC (fixed-dose combination). The identification phase of treatment.4 Many researchers have reported on specific of SNP -25385C>T (rs3814055) was conducted by ARMS (ampli- gene polymorphisms as risk factors for those hepatotoxic effects. – fication refractory mutation system). Hepatotoxicity was defined Some of the reported genes are N-acetyltransferase 2 (NAT2),5 10 as ALT and/or AST levels above the normal threshold on the cytochrome P450 2E1 (CYP2E1),9,11,12 glutathione S-transferase second, fourth and sixth months of monitoring during tubercu- mu-1 (GSTM1)9,10,13 and glutathione S-transferase theta (GSTT).9,13 losis treatment. Other genes also reported to be potential predictors of ATDs-DILI Results and discussion: The logistic regression analysis showed are pregnane X receptor (PXR), glutathione S-transferase alpha-1 that patients with the TT genotype of PXR gene (rs3814055) (GSTA1), manganese superoxide dismutase (MnSOD, SOD2), significantly had a greater risk of AT-DILI (OR 8Á89; 95% CI UDP-glucuronosyltransferase (UGT), nitric oxide synthase 2A 1Á36–57Á93, P < 0Á05), compared with those of wild-type CC (NOS2A), BTB and CNC homology 1 (BACH1), Maf basic leucine – genotype. zipper protein (MAFK), and human leucocyte antigen (HLA).14 18 What is new and conclusion: The result suggests that in We examined PXR gene polymorphism because ligand forma- Indonesian patients with tuberculosis, the risk of having AT- tion between rifampicin and PXR could trigger the expression DILI was associated with TT genotype of the PXR gene. of various genes, including various cytochromes and car- boxylesterases that may be relevant to the metabolism of isoniazid in producing hepatotoxic metabolites. PXR plays a role in the WHAT IS KNOWN AND OBJECTIVE regulation of a number of hepatic and intestine genes involved in Tuberculosis (TB) is an infectious disease that is still a major detoxification and elimination of xenobiotics.19 The polymor- problem in developing countries, including Indonesia. In 2014, the phisms are generally located in the 50-flanking region of the target World Health Organization categorized Indonesia as a high-TB-, genes.20 PXR activates various genes through binding and multi-drug resistant (MDR)-TB-, and human immunodeficiency heterodimer formation with the retinoid X receptor (RXR). PXR virus (HIV)-burdened country. There are an estimated 9Á0 million ligands stimulates the expression of genes involved in xenobiotics incident cases of TB and 1Á5 million people died of the disease each oxidation (phase I), conjugation (phase II) and transport (phase III) year (1Á1 million deaths were HIV negative, and 360 000 were HIV in the liver. PXR is involved in phase I metabolism through the expression of CYP2B6, CYP2C8, CYP2C9, CYP2B9 and – CYP2C19.21 25 Moreover, PXR is involved in phase II metabolism Correspondence: R.
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