Pharmacokinetic study of the novel, synthetic trioxane antimalarial compound 97-78 in rats using an LC-MS/MS method for quantification

Arzneimittel-Forschung/Drug Research

Volumn 61, Issue 2, 2011, Pages 120-125

  Singh, Rajendra Pratap ^a   Sabarinath, S ^a   Gautam, Nagsen ^a   Gupta, Ram Chandra ^a   Singh, Shio Kumar ^a  

^a CENTRAL DRUG RESEARCH INSTITUTE   (India)

Author keywords

1,2,4 Trioxanes; Antimalarial drug 97 78, pharmacokinetics; LC MS MS; Metabolite 97 63

Indexed keywords

1,2,4 TRIOXANE DERIVATIVE; ANTIMALARIAL AGENT; COMPOUND 97 63; COMPOUND 97 78; DRUG METABOLITE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; DRUG BLOOD LEVEL; DRUG ELIMINATION; DRUG HALF LIFE; FEMALE; LIQUID CHROMATOGRAPHY; MALE; MAXIMUM PLASMA CONCENTRATION; MEAN RESIDENCE TIME; NONHUMAN; RAT; TANDEM MASS SPECTROMETRY; TIME TO MAXIMUM PLASMA CONCENTRATION;

EID: 79952334559     PISSN: 00044172     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-0031-1296177     Document Type: Article

References (15)

1. Ashton M, Gordi T, Trinh NH, Nguyen VH, Nguyen DS, Nguyen TN, et al. Artemisinin pharmacokinetics in healthy adults after 250, 500 and 1000 mg single oral doses. Biopharm Drug Dispos. 1998;19:245-50. (Pubitemid 28218419)
2. Li QG, Peggins JO, Fleckenstein LL, Masonic K, Heiffer MH, Brewer TG. The pharmacokinetics and bioavailability of dihydroartemisinin, arteether, artemether, artesunic acid and artelinic acid in rats. J Pharm Pharmacol. 1998;50:173-82. (Pubitemid 28102574)
3. Wu Y. How Might qinghaosu (artemisinin) and related compounds kill the intra-erythrocytic malaria parasite? A chemist's view. Acc Chem Res. 2002;35:255-9.
4. Robert A, Odile DC, Cazelles J, Meunier B. From mechanistic studies on artemisinin derivatives to new modular antimalarial drugs. Acc Chem Res. 2002;35:167-74.
5. Cheng F, Shen J, Luo X, Zhu W, Gu J, Ji R, et al. Molecular docking and 3-D-QSAR studies on the possible antimalarial mechanism of artimisinin analogues. Bioorg Med Chem. 2002;10:2883-91. (Pubitemid 34761866)
6. Singh C, Puri SK, inventors; Council of Scientific and Industrial Research, New Delhi, India, assignee. Substituted 1,2,4-trioxanes as antimalarial agents and a process of producing the substituted 1,2,4-trioxanes. United States patent US 6,316,493 B1. 2001.
7. Singh C, Gupta N, Puri SK. Photo oxygenation of 3-aryl-2-cyclohexenols: synthesis of a new series of antimalarial 1,2,4-trioxanes. Tetrahedron Lett. 2005;46:205.
8. Griesbeck AG, El Idreesy TT, Hoinck LO, Lex J, Brun R. Novel spiroanellated 1,2,4-trioxanes with high in vitro antimalarial activities. Bioorg Med Chem Lett. 2005;15:595-7.
9. Singh C, Srivastava NC, Puri SK. Synthesis and antimalarial activity of 6-cycloalkylvinyl substituted 1,2,4-trioxanes. Bioorg Med Chem. 2004;12:5745-52.
10. Mostafavi SA, Foster RT. Pharmacokinetics of metoprolol enantiomers following single and multiple administration of racemate in rat. Int J Pharm. 2000;202:97-102. (Pubitemid 30466234)
11. Fitoussi S, Thang C, Lesauvage E, Barré J, Charron B, Filali-Ansary A, et al. Bioavailability of a co-formulated combination of amodiaquine and artesunate under fed and fasted conditions a randomised, open-label crossover study. Arzneimittelforschung. 2009;59(7):370-6.
12. Singh RP, Sabarinath S, Gautam N, Gupta RC, Singh SK. Liquid chromatographic tandem mass spectrometric assay for quantification of 97-78 and its metabolite 97-63: a promising trioxane antimalarial in monkey plasma. J Chromatogr B. 2009;877:2074-80.
13. Singh RP, Sabarinath S, Singh SK, Gupta RC. A sensitive and selective liquid chromatographic tandem mass spectrometric assay for simultaneous quantification of novel trioxane antimalarials in different biomatrices using sample-pooling approach for high throughput pharmacokinetic studies. J Chromatogr B. 2008;864:52-60.
14. Waynforth HB. In experimental and surgical technique in the rat. London: Academic Press; 1980. p. 36-46.
15. Griffin RJ, Godfrey VB, Kim YC, Burka LT. Sex-dependent differences in the disposition of 2,4-dichlorophenoxacetic acid in Sprague-Dawley rats, B6C3F1 mice, and Syrian hamsters. Drug Metab Dispos. 1997;25:1065-71. (Pubitemid 27396494)