We evaluated whether sex affects the steady-state pharmacokinetics of the antimalarial drugs, primaquine and doxycycline, in healthy subjects. Seventeen male and 17 female healthy Vietnamese subjects were administered 30 mg (base) of primaquine daily for 14 days. After a 2-week washout period, 14 male and 14 female subjects were administered 100 mg (base) of doxycycline daily for 14 days. Women had significantly higher median values of C(max) (212 versus 122 ng/mL, P< 0.001) and AUC(0-24) (1,909 versus 917 ng . h/mL, P < 0.001) of primaquine compared with men. Other than a longer t(max) in women, no sex-related differences were seen in the pharmacokinetics of doxycycline. The primaquine pharmacokinetic data suggest that women have increased exposure to primaquine, which may put them at increased risk for toxicity when administered the same maintenance dose as men. The similar pharmacokinetics of doxycycline between the two sexes justifies the same maintenance dose.

The two fixed-dose combinations of dihydroartemisinin and piperaquine (Artekin and Arterakine) were found to be bioinequivalent in healthy Vietnamese subjects. However, because the peak plasma concentrations and areas under the concentration-time curves of dihydroartemisinin and piperaquine were only marginally different between the two formulations, similar therapeutic efficacies are expected in the treatment of malaria infections.

We compared plasma maximum concentration (Cmax) and area under the concentration-time curve (AUC) of the antimalarial drug piperaquine in 26 healthy Vietnamese subjects after treatment with either a single oral dose of 500 mg (n = 6) or 1,000 mg (n = 6) of piperaquine phosphate and a three-day course of 500 mg of piperaquine/ day in the fasting state (n = 7) or with food (approximately 17 g fat) (n = 7). The geometric mean plasma Cmax and AUC((0-28)) was 2.8-fold (200 ng/mL versus 70 ng/mL) and 1.9-fold (5,736 ng x h/mL versus 2,999 ng x h/mL), respectively, and higher in subjects receiving the 1,000-mg dose than in those receiving the 500-mg dose. The geometric mean Cmax and AUC((0-28)) was 1.7-fold (198 ng/mL versus 119 ng/mL) and 1.4-fold (11,187 ng x h/mL versus 7,954 ng x h/mL) higher in the fed state than in the fasting state. Piperaquine AUC was proportional to the two doses tested and a moderate-fat meal enhanced the bioavailability of piperaquine by 41%, which should improve the therapeutic efficacy of this drug.

In 18 male healthy subjects, artesunate (200 mg)-azithromycin (1,500 mg) daily for 3 days was found to be well tolerated, with only mild gastrointestinal disturbances reported. The pharmacokinetic properties of artesunate-azithromycin given in combination are comparable to those of the drugs given alone. Artesunate and its major active metabolite, dihydroartemisinin, are responsible for most of the ex vivo antimalarial activity, with a delayed contribution by azithromycin.Artemisinin-based combination therapies (ACTs) are currently recommended for the first-line treatment of uncomplicated Plasmodium falciparum malaria, worldwide (25). The two risk groups most vulnerable to malaria are young children and pregnant women, who are immunosuppressed and particularly at risk for severe disease (26). In pregnant women, limited safety and pharmacological data are available on the use of ACTs, particularly during the first trimester. The World Health Organization (WHO) recommends that quinine combined with the antibiotic clindamycin be given for 7 days during the first trimester and, if quinine-clindamycin is either unavailable or fails, an ACT is indicated (25). Historically, 7-day daily regimens are limited by poor compliance in an outpatient setting (9). For the second and third trimesters, WHO recommends artesunate (AS)-clindamycin.However, a drawback in using clindamycin is its short halflife of 2.4 h (10), which necessitates repeated dosing every 12 h, which may affect compliance and thus effectiveness (20). Unlike clindamycin, the antibiotic azithromycin (AZ) possesses wider therapeutic applications (8) and has pharmacokinetic properties that are characterized by more extensive tissue distribution, prolonged phagocyte concentrations, and a longer elimination half-life of about 50 h (1, 14). These favorable features allow once-daily dosing with AZ compared with multiple daily dosing with clindamycin. Recently, 3-day courses of quinine with either 1,000 or 1,500 mg AZ were shown to be well tolerated and effective in curing multidrug-resistant P. falciparum malaria in adults (12). AZ also has a good safety profile in children and pregnant women (6, 21).Because of AZ's favorable pharmacokinetic properties, artesunate (AS) plus AZ may be a suitable ACT during pregnancy. In vitro studies have shown dihydroartemisinin (DHA), the active metabolite of the prodrug AS, combined with AZ to be additive (17) tending to synergistic (16) against multidrugresistant P. falciparum strains. Recent studies of AS-AZ have shown good efficacy in the treatment of uncomplicated falciparum malaria using 3-day regimens of 200 mg AS daily with either 1,000 mg AZ (cure rate, 89%) (15) or 1,500 mg AZ (cure rates, Ͼ92%) (15, 24). The AS-AZ combinations are far more effective than monotherapy, with recrudescence rates of between 10% and 80% with 3-to 5-day courses of AS alone (4) and 67% with 1,000 mg/day AZ for 3 days (7). Similarly, the addition of AZ (1,000 mg daily for 2 days) to 1,500 mg sulfadoxine and 75 mg pyrimethamine for the treatment o...

China is a sleeping giant. Let her sleep, for when she wakes, she will shake the world” - Napoleon Bonaparte. The rise of China is a phenomenon in the 21st century. The rise of China is one of the most significant contributions to the restructuring of the world order as well as the Asian Pacific order. Although the United States remains one of the most powerful countries in the world, its regional and global hegemony has been considerably challenged by China. This paper contains three main objectives: (1) to present an overview on the miraculous growth of Chinese economy; (2) to identify the challenges from China’s rise posing on the regional and international system; and (3) to make an analysis on the case of the South China Sea disputes in order to clarify the reaction of the system towards the China’s rise