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Proguanil, poor metabolism of

MedGen UID:
322804
•Concept ID:
C1836026
•
Finding
Synonym: Proguanil, Poor Metabolism of
 
OMIM®: 124020; 609535

Professional guidelines

PubMed

Pharmacogenetics of drug oxidation via cytochrome P450 (CYP) in the populations of Denmark, Faroe Islands and Greenland.
Brosen K
Drug Metab Pers Ther 2015 Sep;30(3):147-63. doi: 10.1515/dmdi-2014-0029. PMID: 25719307
Pheno- or genotype for the CYP2C19 drug metabolism polymorphism: the influence of disease.
Helsby NA
Proc West Pharmacol Soc 2008;51:5-10. PMID: 19544664
Clinical pharmacokinetics in the treatment of tropical diseases. Some applications and limitations.
Edwards G, Winstanley PA, Ward SA
Clin Pharmacokinet 1994 Aug;27(2):150-65. doi: 10.2165/00003088-199427020-00006. PMID: 7955777

Recent clinical studies

Etiology

Randomized trial of safety and effectiveness of chlorproguanil-dapsone and lumefantrine-artemether for uncomplicated malaria in children in the Gambia.
Dunyo S, Sirugo G, Sesay S, Bisseye C, Njie F, Adiamoh M, Nwakanma D, Diatta M, Janha R, Sisay Joof F, Temple B, Snell P, Conway D, Walton R, Cheung YB, Milligan P
PLoS One 2011;6(6):e17371. Epub 2011 Jun 7 doi: 10.1371/journal.pone.0017371. PMID: 21666744Free PMC Article
Clinical significance of the cytochrome P450 2C19 genetic polymorphism.
Desta Z, Zhao X, Shin JG, Flockhart DA
Clin Pharmacokinet 2002;41(12):913-58. doi: 10.2165/00003088-200241120-00002. PMID: 12222994
Clinical relevance of genetic polymorphisms in the human CYP2C subfamily.
Goldstein JA
Br J Clin Pharmacol 2001 Oct;52(4):349-55. doi: 10.1046/j.0306-5251.2001.01499.x. PMID: 11678778Free PMC Article
Populations and genetic polymorphisms.
Weber WW
Mol Diagn 1999 Dec;4(4):299-307. doi: 10.154/MODI00400299. PMID: 10671640
Japanese poor metabolizers of proguanil do not have an increased risk of malaria chemoprophylaxis breakthrough.
Mberu EK, Wansor T, Sato H, Nishikawa Y, Watkins WM
Trans R Soc Trop Med Hyg 1995 Nov-Dec;89(6):658-9. doi: 10.1016/0035-9203(95)90434-4. PMID: 8594689

Diagnosis

Populations and genetic polymorphisms.
Weber WW
Mol Diagn 1999 Dec;4(4):299-307. doi: 10.154/MODI00400299. PMID: 10671640
Proguanil polymorphism does not affect the antimalarial activity of proguanil combined with atovaquone in vitro.
Edstein MD, Yeo AE, Kyle DE, Looareesuwan S, Wilairatana P, Rieckmann KH
Trans R Soc Trop Med Hyg 1996 Jul-Aug;90(4):418-21. doi: 10.1016/s0035-9203(96)90531-3. PMID: 8882194
Chloroguanide metabolism in relation to the efficacy in malaria prophylaxis and the S-mephenytoin oxidation in Tanzanians.
Skjelbo E, Mutabingwa TK, Bygbjerg Ib, Nielsen KK, Gram LF, Brøosen K
Clin Pharmacol Ther 1996 Mar;59(3):304-11. doi: 10.1016/S0009-9236(96)80008-7. PMID: 8653993
Chloroquine-induced inhibition of the production of TNF, but not of IL-6, is affected by disruption of iron metabolism.
Picot S, Peyron F, Donadille A, Vuillez JP, Barbe G, Ambroise-Thomas P
Immunology 1993 Sep;80(1):127-33. PMID: 8244453Free PMC Article
Variability in the metabolism of proguanil to the active metabolite cycloguanil in healthy Kenyan adults.
Watkins WM, Mberu EK, Nevill CG, Ward SA, Breckenridge AM, Koech DK
Trans R Soc Trop Med Hyg 1990 Jul-Aug;84(4):492-5. doi: 10.1016/0035-9203(90)90010-c. PMID: 2091335

Therapy

Randomized trial of safety and effectiveness of chlorproguanil-dapsone and lumefantrine-artemether for uncomplicated malaria in children in the Gambia.
Dunyo S, Sirugo G, Sesay S, Bisseye C, Njie F, Adiamoh M, Nwakanma D, Diatta M, Janha R, Sisay Joof F, Temple B, Snell P, Conway D, Walton R, Cheung YB, Milligan P
PLoS One 2011;6(6):e17371. Epub 2011 Jun 7 doi: 10.1371/journal.pone.0017371. PMID: 21666744Free PMC Article
Population pharmacokinetics of proguanil in patients with acute P. falciparum malaria after combined therapy with atovaquone.
Hussein Z, Eaves CJ, Hutchinson DB, Canfield CJ
Br J Clin Pharmacol 1996 Nov;42(5):589-97. doi: 10.1111/j.1365-2125.1996.tb00114.x. PMID: 8951190
Proguanil polymorphism does not affect the antimalarial activity of proguanil combined with atovaquone in vitro.
Edstein MD, Yeo AE, Kyle DE, Looareesuwan S, Wilairatana P, Rieckmann KH
Trans R Soc Trop Med Hyg 1996 Jul-Aug;90(4):418-21. doi: 10.1016/s0035-9203(96)90531-3. PMID: 8882194
Clinical pharmacokinetics in the treatment of tropical diseases. Some applications and limitations.
Edwards G, Winstanley PA, Ward SA
Clin Pharmacokinet 1994 Aug;27(2):150-65. doi: 10.2165/00003088-199427020-00006. PMID: 7955777
Single dose pharmacokinetics of proguanil and its metabolites in pregnancy.
Wangboonskul J, White NJ, Nosten F, ter Kuile F, Moody RR, Taylor RB
Eur J Clin Pharmacol 1993;44(3):247-51. doi: 10.1007/BF00271366. PMID: 8491239

Prognosis

Randomized trial of safety and effectiveness of chlorproguanil-dapsone and lumefantrine-artemether for uncomplicated malaria in children in the Gambia.
Dunyo S, Sirugo G, Sesay S, Bisseye C, Njie F, Adiamoh M, Nwakanma D, Diatta M, Janha R, Sisay Joof F, Temple B, Snell P, Conway D, Walton R, Cheung YB, Milligan P
PLoS One 2011;6(6):e17371. Epub 2011 Jun 7 doi: 10.1371/journal.pone.0017371. PMID: 21666744Free PMC Article
Analysis of Sepik populations of Papua New Guinea suggests an increase of CYP2C19 null allele frequencies during the colonization of Melanesia.
Masta A, Lum JK, Tsukahara T, Hwaihwanje I, Kaneko A, Paniu MM, Sapuri M, Takahashi N, Ishizaki T, Kobayakawa T, Hombhanje FW
Pharmacogenetics 2003 Nov;13(11):697-700. doi: 10.1097/00008571-200311000-00006. PMID: 14583683
Identification and functional characterization of new potentially defective alleles of human CYP2C19.
Blaisdell J, Mohrenweiser H, Jackson J, Ferguson S, Coulter S, Chanas B, Xi T, Ghanayem B, Goldstein JA
Pharmacogenetics 2002 Dec;12(9):703-11. doi: 10.1097/00008571-200212000-00004. PMID: 12464799
Clinical significance of the cytochrome P450 2C19 genetic polymorphism.
Desta Z, Zhao X, Shin JG, Flockhart DA
Clin Pharmacokinet 2002;41(12):913-58. doi: 10.2165/00003088-200241120-00002. PMID: 12222994
High and variable frequencies of CYP2C19 mutations: medical consequences of poor drug metabolism in Vanuatu and other Pacific islands.
Kaneko A, Lum JK, Yaviong L, Takahashi N, Ishizaki T, Bertilsson L, Kobayakawa T, Björkman A
Pharmacogenetics 1999 Oct;9(5):581-90. PMID: 10591538

Clinical prediction guides

Effects of Biguanides on Growth and Glycolysis of Bladder and Colon Cancer Cells.
Lea MA, Kim H, desBORDES C
Anticancer Res 2018 Sep;38(9):5003-5011. doi: 10.21873/anticanres.12819. PMID: 30194144
Identification and functional characterization of new potentially defective alleles of human CYP2C19.
Blaisdell J, Mohrenweiser H, Jackson J, Ferguson S, Coulter S, Chanas B, Xi T, Ghanayem B, Goldstein JA
Pharmacogenetics 2002 Dec;12(9):703-11. doi: 10.1097/00008571-200212000-00004. PMID: 12464799
Clinical significance of the cytochrome P450 2C19 genetic polymorphism.
Desta Z, Zhao X, Shin JG, Flockhart DA
Clin Pharmacokinet 2002;41(12):913-58. doi: 10.2165/00003088-200241120-00002. PMID: 12222994
Intrinsic efficacy of proguanil against falciparum and vivax malaria independent of the metabolite cycloguanil.
Kaneko A, Bergqvist Y, Takechi M, Kalkoa M, Kaneko O, Kobayakawa T, Ishizaki T, Björkman A
J Infect Dis 1999 Apr;179(4):974-9. doi: 10.1086/314683. PMID: 10068594
Chloroquine-induced inhibition of the production of TNF, but not of IL-6, is affected by disruption of iron metabolism.
Picot S, Peyron F, Donadille A, Vuillez JP, Barbe G, Ambroise-Thomas P
Immunology 1993 Sep;80(1):127-33. PMID: 8244453Free PMC Article

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