Disease relevance of proguanil

• Atovaquone-proguanil (Malarone; GlaxoSmithKline) was safe and effective for prevention of falciparum malaria in lifelong residents of malaria-endemic countries, but experience in nonimmune people is limited [1].
• The protective efficacy of Malarone for all malaria and for P. vivax malaria was 100% (LL 95% CI = 63%) and 100% (LL 95% CI = 58%), respectively, and was 96% if the one case with undetectable blood levels was included [2].
• Stevens-Johnson syndrome associated with Malarone antimalarial prophylaxis [3].
• The P. falciparum recrudescence rate was lower with the use of Malarone than for quinine [4].

Psychiatry related information on proguanil

• The impact of Malarone and primaquine on psychomotor performance [5].

High impact information on proguanil

• BACKGROUND: Two single-point mutations of the Plasmodium falciparum cytochrome b gene (Tyr268Asn and Tyr268Ser) were recently reported in cases of atovaquone/proguanil (Malarone) treatment failure [6].
• These results suggest that even the best of the repository preparations of CGT-P, with or without 4,4'-diacetyldiaminodiphenylsulfone, would be useful only in areas where Plasmodium falciparum and Plasmodium vivax are fully susceptible to chlorguanide and pyrimethamine [7].
• Malarone (atovaquone and proguanil hydrochloride): a review of its clinical development for treatment of malaria. Malarone Clinical Trials Study Group [8].
• Despite the use of only small quantities of chlorguanide and/or quinine to control infection coupled with the use of small inocula and delays in splenectomy, mosquito infection was markedly reduced from that seen during primary passage to this species of Aotus [9].
• OBJECTIVE: To investigate the pharmacokinetics, safety and efficacy of the recommended 3-day treatment regimen of Malarone in third-trimester pregnant women with acute uncomplicated falciparum malaria [10].

Chemical compound and disease context of proguanil

• The combination of atovaquone and proguanil (Malarone) has become established as an agent of choice to prevent and treat chloroquine-resistant Plasmodium falciparum malaria in travelers [11].
• BACKGROUND: Previous experience with unacceptable adverse effects with mefloquine as treatment for uncomplicated Plasmodium falciparum malaria prompted an evaluation of the effectiveness and side effects of atovaquone-proguanil (Malarone) in a hospital setting [12].
• Uncomplicated P. falciparum malaria can be treated orally with quinine, atovaquone plus proguanil (Malarone) or co-artemether (Riamet); quinine is highly effective but poorly tolerated in prolonged dosage and is always supplemented by additional treatment, usually with oral doxycycline [13].
• The recently licensed fixed combination of atovaquone and proguanil hydrochloride (Malarone) is a promising new agent to prevent and treat Plasmodium falciparum malaria [14].

Biological context of proguanil

• Time-dependent pharmacokinetics and drug metabolism of atovaquone plus proguanil (Malarone) when taken as chemoprophylaxis [15].
• BACKGROUND: Atovaquone is part of the antimalarial drug combination atovaquone-proguanil (Malarone) and inhibits the cytochrome bc1 complex of the electron transport chain in Plasmodium spp [16].

Anatomical context of proguanil

• One month after starting donepezil HCl (10 mg/day), sensorimotor function improved dramatically in the hemiplegic lower limb and shoulder [17].

Associations of proguanil with other chemical compounds

• Selegiline hydrochloride (HCl) undergoes significant first-pass metabolism following oral administration [18].

Gene context of proguanil

• Sera from patients treated with atovaquone-proguanil (Malarone) have previously been shown to inhibit the mosquito transmission of Plasmodium falciparum, though the inhibition was not complete and the effect declined 2 weeks after treatment [19].
• Malarone treatment failure not associated with previously described mutations in the cytochrome b gene [20].
• Additionally, we investigated the parasite cytochrome b gene of a patient returning from Mali with Malarone treatment failure in vivo [21].

Analytical, diagnostic and therapeutic context of proguanil

• Atovaquone-proguanil versus chloroquine-proguanil for malaria prophylaxis in non-immune travellers: a randomised, double-blind study. Malarone International Study Team [22].
• Thus, Malarone appears to have an excellent safety and efficacy profile for the chemoprophylaxis of P. falciparum infection [23].
• AP is no longer available through the Malarone Donation Programme and is too expensive for routine use in Africa. However, this study has shown that in an area with a modest level of resistance to SP, use of a more effective antimalaria reduces the need for blood transfusion in children with malarial anaemia [24].
• An isocratic high-performance liquid chromatographic (HPLC) method for simultaneous separation of the components in the antimalarial combination drug Malarone with UV detection is described [25].
• METHOD: Twenty-eight subjects (20 men and 8 women) ranging from 21 to 52 yr of age were assessed for psychomotor performance on 2 psychomotor test batteries at the end of a 7-d dosing protocol for each of placebo, Malarone, and primaquine treatment, in a double-blind crossover design with counterbalanced treatment order [5].

References