Edstein, M DLooareesuwan, SViravan, CKyle, D E2009-05-272009-05-271996-06-01Edstein MD, Looareesuwan S, Viravan C, Kyle DE. Pharmacokinetics of proguanil in malaria patients treated with proguanil plus atovaquone. The Southeast Asian Journal of Tropical Medicine and Public Health. 1996 Jun; 27(2): 216-20http://imsear.searo.who.int/handle/123456789/31741The Southeast Asian Journal of Tropical Medicine and Public Health.Clinical studies have shown atovaquone (ATQ), a new blood schizontocidal drug, in combination with proguanil (PROG) to be very effective in the treatment of acute multidrug-resistant falciparum malaria. The multiple dose pharmacokinetics of PROG were determined in Thai patients with acute falciparum malaria given PROG alone (200 mg PROG twice a day for 3 days, n = 4) and concurrently PROG and ATQ (200 mg PROG and 500 mg ATQ twice a day for 3 days, n = 12). There were no statistical differences (p > 0.05) in the area under the plasma drug concentration-time curve (AUC), apparent oral clearance (CL/F) and elimination half-life (t1/2) of PROG between patients given PROG alone and PROG/ ATQ. The median (range) kinetic values of PROG in patients given PROG alone and PROG/ATQ were respectively: CL/F = 1.25 l/h/kg (0.99-1.45) and 0.95 (0.73-1.32) l/h/kg, and t1/2 = 14.2 hours (9.3-16.8) and 13.6 hours (9.1-17.6). The CL/F and t1/2 of PROG in the Thai patients treated with the 2 treatment regimens were also comparable to values reported in healthy Thai volunteers given a standard prophylactic dose (200 mg PROG). The results of this preliminary study suggest that ATQ is unlikely to affect the pharmacokinetics of PROG to a clinically important extent at an ATQ dosage of 500 mg twice a day for 3 days in malaria infected patients.engAcute DiseaseAdolescentAdultAntimalarials --pharmacokineticsAtovaquoneChloroguanide --pharmacokineticsDose-Response Relationship, DrugDrug Resistance, MultipleDrug SynergismDrug Therapy, CombinationHumansIntestinal AbsorptionMalaria, Falciparum --drug therapyMaleMetabolic Clearance RateNaphthoquinones --pharmacokineticsClinical Trial