Soluble MICB protein levels and platelet counts during hepatitis B virus infection and response to hepatocellular carcinoma treatment.

BACKGROUND: The human major histocompatibility complex class I polypeptide-related sequence B (MICB) is a protein that modulates the NK and T cell activation through the NKG2D receptor and is related to several diseases including cancer. METHODS: The study investigated the prognostic role of soluble MICB (sMICB) protein in the progression of HBV-related liver diseases and to HBV-related HCC treatment. The sMICB serum levels were measured in 266 chronic HBV-infected Vietnamese patients and in healthy controls, and correlated with clinical and laboratory parameters and with therapeutic interventions for HBV-related HCC. RESULTS: Significant differences in both clinical and laboratory parameters were observed among the patient groups with different stages of hepatitis. The platelet counts were significantly decreased with disease progression (P < 0.001). The sMICB serum levels were significantly increased in HBV patients compared to healthy controls (P < 0.0001). Among the patients with different stages of hepatitis, asymptomatic individuals (ASYM) revealed higher sMICB serum levels while liver cirrhosis (LC) patients revealed lower sMICB serum levels (P < 0.0001) compared to other patient groups. Notably, the sMICB serum levels were decreased in treated HCC patient group compared to not-treated HCC patient group (P = 0.05). Additionally, the sMICB levels were significantly correlated with platelet counts in ASYM and HCC patients (r = -0.37, P = 0.009; and r = 0.22, P = 0.025, respectively). CONCLUSIONS: Our results demonstrate a potential role of sMICB serum levels and platelet counts during immune response to the HBV infection, liver disease progression and response to the HCC treatment.

Sex affects the steady-state pharmacokinetics of primaquine but not doxycycline in healthy subjects.

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.

Does gender, food or grapefruit juice alter the pharmacokinetics of primaquine in healthy subjects?

AIMS: To evaluate the effects of gender, food and grapefruit juice on the pharmacokinetics of primaquine in healthy subjects. METHODS: In a randomized, two-phase cross-over study, 10 male and 10 female healthy Vietnamese subjects were administered 30 mg primaquine in the fasting state or with food, followed by administration of primaquine with grapefruit juice. RESULTS: The pharmacokinetics of primaquine were comparable between male and female subjects, with geometric mean ratios of Cmax = 0.89 [95% confidence interval (CI) 0.65, 1.22] and AUC = 0.80 (95% CI 0.56, 1.15). The mean CL/F of primaquine was slightly higher in males than in females [0.52 l h(-1) kg(-1)vs. 0.43 l h(-1) kg(-1), mean difference of 0.09 (95% CI -0.10, 0.28), P = 0.32]. When compared with fasting state values, food increased the geometric mean Cmax of primaquine by 26% (95% CI 12, 40) and the AUC by 14% (95% CI 3, 27). Similarly, grapefruit juice increased the geometric mean Cmax by 23% (95% CI 4, 45) and the AUC by 19% (95% CI 4, 37). CONCLUSIONS: The disposition of primaquine was comparable between genders, suggesting no need to modify the dose of primaquine for malaria treatment or prophylaxis. Food increased the oral bioavailability of primaquine, which may lead to higher antimalarial efficacy. Grapefruit juice increased the bioavailability of primaquine, with marked interindividual differences suggesting that people should not take primaquine with grapefruit juice.

Fatty food does not alter blood mefloquine concentrations in the treatment of falciparum malaria.

Food has been reported to increase the bioavailability of mefloquine in healthy volunteers, but its role in increasing blood mefloquine concentrations in malaria patients treated with mefloquine is unclear. In this study, we compared blood mefloquine concentrations after the administration of artesunate (8 mg/kg) and mefloquine (15 mg/kg) over 12h with either a low-fat (approximately 3g of fat) or high-fat (approximately 30 g of fat) meal for the treatment of Plasmodium falciparum malaria in 12 Vietnamese patients. No statistical differences were detected in the following kinetic parameters between the low-fat (n=6) and high-fat (n=6) groups, respectively: maximum blood mefloquine concentrations (2838+/-531 ng/ml and 2556+/-657 ng/ml, 95% CI -486 to 1050 ng/ml, P=0.43) and the area under the blood mefloquine concentration versus time curves (246.8+/-58.3 microg.h/ml and 238.3+/-28.4 microg.h/ml, 95% CI -50.5 to 67.5 microg.h/ml, P=0.75). A fatty meal does not appear to increase the bioavailability of mefloquine in malaria patients and should not affect the response of malaria infections to treatment.