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Untoward effects on the QTc interval are unlikely to occur when co-artemether is administered following prophylaxis or treatment with mefloquine.

The therapeutic efficacy and safety of ciprofloxacin was studied in 30 patients with Pseudomonas aeruginosa infections. In 20 patients ciprofloxacin was given alone and in 10 patients (including 8 compromised hosts) in combination with an aminoglycoside (9) or azlocillin (1). Ciprofloxacin was given in doses of 500 mg orally or 200-300 mg i.v. every 12 h. In patients receiving only ciprofloxacin clinical cure with eradication of bacteria was obtained in 15 patients (75%) with infections of bone and joint (6), skin and soft tissue (4), lung (2), middle ear (2) and CSF (1). Two patients with lymphoma and Pseudomonas aeruginosa pneumonia died. In patients receiving combination therapy a definite therapeutic success was achieved in four (40%). Three patients with Pseudomonas aeruginosa septicemia died. In seven patients nine bacterial strains with decreasing susceptibility of ciprofloxacin (increase in MIC from less than or equal to 0.5 micrograms/ml to 2-16 micrograms/ml) were selected (6 Pseudomonas aeruginosa, 1 Enterobacter cloacae, 1 Serratia marcescens, 1 Staphylococcus aureus). Ciprofloxacin was well tolerated. This new quinolone seems to be suitable for single drug treatment of Pseudomonas aeruginosa infections in patients with normal host defense mechanisms, while its therapeutic potential in compromised hosts requires further evaluation.

Abstract. Co-artemether (Coartem, Riamet) is a tablet containing 20 mg artemether and 120 mg lumefantrine for treatment of falciparum malaria. Lumefantrine has some chemical similarities to halofantrine (Halfan), an antimalarial known for QTc prolongation. Effects on the QTc interval of fed single oral doses of 500 mg halofantrine and 80/480 mg co-artemether were compared in 13 healthy males in a randomized double-blind crossover study. Electrocardiograms (ECGs) were recorded from 48 hours before dosing until 48 hours thereafter. The maximum QTc interval (QTc ‫ס‬ QT/√RR) was compared before and after treatment and between treatments, fitting a general linear model. Drug plasma concentrations were determined concomitantly. After halofantrine, all participants showed an increase in the QTc interval; the mean maximum increase was 28 ms. The length of the QTc interval was positively correlated to halofantrine exposure. The QTc interval remained unchanged after co-artemether. The difference between treatments was statistically significant. In conclusion, halofantrine caused a significant, exposure-dependent increase in the QTc interval. No such effect was seen with co-artemether.Malaria is the cause of considerable morbidity and mortality in the developing world, and there is a clear need for new treatments, particularly as resistance to available drugs is increasing. 1,2Co-artemether (Coartem, Riamet), which was developed in China for the treatment of falciparum malaria, is an oral preparation containing 20 mg artemether and 120 mg lumefantrine (previously known as benflumetol) per tablet. Artemether, an artemisinin derivative, is characterized by a rapid onset of schizontocidal action resulting in fast relief from fever and fast parasite clearance. However, recrudescence is frequent when provided as a single agent, unless given for at least 5-7 days.3-6 By contrast, lumefantrine has a high cure rate when administered as a short treatment course of 2-3 days duration, but parasite and fever clearance is much slower than with artemether. Co-artemether combines the treatment advantages of both drugs, providing a short and simple antimalarial treatment likely to improve compliance. In areas of multidrug resistance and in nonimmune patients, the recommended dose regimen is 6 doses of 4 tablets each (80 mg artemether and 480 mg lumefantrine per dose) given over 60 hours. Otherwise, the recommended dose regimen is 4 doses of 4 tablets over 2 days.Halofantrine (Halfan) is one of the antimalarial compounds causing QTc prolongation at standard therapeutic doses (3 doses of 500 mg given at 6-hour intervals). Because lumefantrine has some chemical similarities to halofantrine, and QTc prolongation was reported after high-dose intramuscular treatment with artemether in animal experiments 7 and in a clinical study in patients with severe malaria, 8 a careful evaluation of co-artemether with regard to cardiac effects, particularly on the QTc interval, was warranted.In the current study, the potential cardiac effects of coartemethe...

Simultaneous administration of valsartan and furosemide did not modify the pharmacokinetics of valsartan. In contrast, Cmax, AUC, and urinary excretion of furosemide were significantly reduced following simultaneous treatment with valsartan. Inter- and intra-individual variability of the pharmacokinetic variables was high for both furosemide and valsartan. PRA and angiotensin II increased, and blood pressure decreased after all treatments. These effects were most pronounced after the combined treatment. The decrease in blood pressure was additive, at most, while the increase in PRA and angiotensin II appeared to exceed simple addition. No relevant effects on heart rate were observed. The diuretic effect of furosemide, as assessed by urinary water and electrolyte excretion, was unchanged after co-administration of valsartan, despite the lower bioavailability of furosemide after the combined treatment.

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