Tafenoquine

Tafenoquine
Clinical data
Other names	Etaquine, WR 238605, SB-252263
ATC code	none;
Identifiers
	IUPAC name N-[2,6-Dimethoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]quinolin-8-yl]pentane-1,4-diamine;
CAS Number	106635-80-7 ;
PubChem CID	115358;
ChemSpider	103196 ;
UNII	262P8GS9L9;
KEGG	D10490 ;
ChEBI	CHEBI:135752;
ChEMBL	ChEMBL298470 ;
NIAID ChemDB	006901;
CompTox Dashboard (EPA)	DTXSID90869466 ;
Chemical and physical data
Formula	C24H28F3N3O3
Molar mass	463.493 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES FC(F)(F)c3cc(Oc1c(OC)cc(NC(C)CCCN)c2nc(OC)cc(c12)C)ccc3;
	InChI InChI=1S/C24H28F3N3O3/c1-14-11-20(32-4)30-22-18(29-15(2)7-6-10-28)13-19(31-3)23(21(14)22)33-17-9-5-8-16(12-17)24(25,26)27/h5,8-9,11-13,15,29H,6-7,10,28H2,1-4H3 ; Key:LBHLFPGPEGDCJG-UHFFFAOYSA-N ;
	(what is this?) (verify)

Tafenoquine under the commercial name of Krintafel is an 8-aminoquinoline drug manufactured by GlaxoSmithKline that is being investigated as a potential treatment for malaria, as well as for malaria prevention.^[2]^[3]

The proposed indication for tafenoquine is for treatment of the hypnozoite stages of Plasmodium vivax and Plasmodium ovale that are responsible for relapse of these malaria species even when the blood stages are successfully cleared. This is only now achieved by administration of daily primaquine for 14 days. The main advantage of tafenoquine is that it has a long half-life (2–3 weeks) and therefore a single treatment may be sufficient to clear hypnozoites. The shorter regimen has been described as an advantage.^[4]

Like primaquine, tafenoquine causes hemolysis in people with G6PD deficiency.^[2] Indeed, the long half-life of tafenoquine suggests that particular care should be taken to ensure that individuals with severe G6PD deficiency do not receive the drug.

The dose of tafenoquine has not been firmly established, but for the treatment of Plasmodium vivax malaria, a dose of 800 mg over three days has been used.^[5]

In 2018 United States Food and Drug Administration (FDA) approved single dose tafenoquine for the radical cure (prevention of relapse) of Plasmodium vivax malaria^[6].

Stereochemistry

Tafenoquine contains a stereocenter and consists of two enantiomers. This is a mixture of (R) - and the (S) - Form:

Enantiomers of tafenoquine
(R)-Form	(S)-Form

References

^ ^a ^b Peters W (1999). "The evolution of tafenoquine--antimalarial for a new millennium?". J R Soc Med. 92 (7): 345–352. PMC 1297286. PMID 10615272.
^ ^a ^b Shanks GD; Oloo AJ; Aleman GM; et al. (2001). "A New Primaquine Analogue, Tafenoquine (WR 238605), for prophylaxis against Plasmodium falciparum malaria". Clin Infect Dis. 33 (12): 1968–74. doi:10.1086/324081. JSTOR 4482936. PMID 11700577. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ Lell B; Faucher JF; Missinou MA; et al. (2000). "Malaria chemoprophylaxis with tafenoquine: a randomised study". Lancet. 355 (9220): 2041–5. doi:10.1016/S0140-6736(00)02352-7. PMID 10885356. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
^ Elmes NJ, Nasveld PE, Kitchener SJ, Kocisko DA, Edstein MD (November 2008). "The efficacy and tolerability of three different regimens of tafenoquine versus primaquine for post-exposure prophylaxis of Plasmodium vivax malaria in the Southwest Pacific". Transactions of the Royal Society of Tropical Medicine and Hygiene. 102 (11): 1095–101. doi:10.1016/j.trstmh.2008.04.024. PMID 18541280.
^ Nasveld P, Kitchener S (2005). "Treatment of acute vivax malaria with tafenoquine". Trans R Soc Trop Med Hyg. 99 (1): 2–5. doi:10.1016/j.trstmh.2004.01.013. PMID 15550254.
^ "Drugs@FDA: FDA Approved Drug Products". www.accessdata.fda.gov. Retrieved 2018-07-23.

[Peters1999-1] Peters W (1999). "The evolution of tafenoquine--antimalarial for a new millennium?". J R Soc Med. 92 (7): 345–352. PMC 1297286. PMID 10615272.

[Shanks2001-2] Shanks GD; Oloo AJ; Aleman GM; et al. (2001). "A New Primaquine Analogue, Tafenoquine (WR 238605), for prophylaxis against Plasmodium falciparum malaria". Clin Infect Dis. 33 (12): 1968–74. doi:10.1086/324081. JSTOR 4482936. PMID 11700577. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[3] Lell B; Faucher JF; Missinou MA; et al. (2000). "Malaria chemoprophylaxis with tafenoquine: a randomised study". Lancet. 355 (9220): 2041–5. doi:10.1016/S0140-6736(00)02352-7. PMID 10885356. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)

[pmid18541280-4] Elmes NJ, Nasveld PE, Kitchener SJ, Kocisko DA, Edstein MD (November 2008). "The efficacy and tolerability of three different regimens of tafenoquine versus primaquine for post-exposure prophylaxis of Plasmodium vivax malaria in the Southwest Pacific". Transactions of the Royal Society of Tropical Medicine and Hygiene. 102 (11): 1095–101. doi:10.1016/j.trstmh.2008.04.024. PMID 18541280.

[5] Nasveld P, Kitchener S (2005). "Treatment of acute vivax malaria with tafenoquine". Trans R Soc Trop Med Hyg. 99 (1): 2–5. doi:10.1016/j.trstmh.2004.01.013. PMID 15550254.

[6] "Drugs@FDA: FDA Approved Drug Products". www.accessdata.fda.gov. Retrieved 2018-07-23.

[1]

[2]

[3]

[4]

[5]

[6]