Drug interaction between St John's wort and zolpidem in healthy subjects.

WHAT IS KNOWN AND OBJECTIVE: St John's wort (SJW, Hypericum perforatum) is one of the most commonly used herbal antidepressants for treatment of mild to moderate depression. SJW enhances CYP3A4 activity and alters the pharmacokinetics of CYP3A4 substrates. This study investigated the effect of SJW on the pharmacokinetics of zolpidem in healthy subjects. METHODS: A controlled, open-label, non-randomized, fixed-dose schedule design was used. Fourteen healthy male subjects received a single 10 mg oral dose of zolpidem followed by SJW administration (300 mg orally, three times a day) for 14 days; the last dose of SJW was coadministered with a single dose of zolpidem. Blood samples were obtained over a 24-h period after zolpidem administration. Pharmacokinetic data for zolpidem alone and in combination with SJW were analysed by high-performance liquid chromatography. RESULTS: After repeated administration of SJW, the mean values of AUC and C(max) for zolpidem significantly decreased (380.3 ± 181.4 vs. 265.4 ± 134.2 ng h/mL, P = 0.001; 83.1 ± 30.1 vs. 55.1 ± 24.8 ng/mL, P = 0.000 respectively) and the mean value of CL/F for zolpidem significantly increased (38.4 ± 31.5 vs. 56.9 ± 57.2 mL/min, P = 0.040). However, in three subjects, the AUC showed a small increase after SJW treatment. WHAT IS NEW AND CONCLUSION: The effect of SJW on the pharmacokinetics of zolpidem has not previously been reported. Repeated administration of SJW decreases the plasma concentration of zolpidem, probably by enhancing CYP3A4 activity. Given the wide inter-subject variability observed, for personalized medicine, advice on the use of the combination should be individualized, based on the circumstances of the patient.

[In vivo toxicity, and glutathione, ascorbic acid and copper level changes induced in mouse liver and kidney by copper(II) gluconate, a nutrient supplement].

While copper(II) gluconate (CuGL) is generally used as a nutrient supplement for infant foods and as an oral deodorant, little information is available regarding a toxic effect of CuGL on mammals. In this article, we examined in vivo induction of toxicity and change of level of glutathione and ascorbic acid, major biological antioxidants, lipid peroxide and copper (Cu) in liver and kidney 4 h after single intraperitoneal administration of CuGL at 0.05 and 0.10 mmol/kg to mice. Serum glutamic pyruvic transaminase (SGPT) activity, an indicator of hepatotoxicity, significantly increased compared to control in proportion to doses of CuGL. Hepatic level of glutathione measured as nonprotein sulfhydryl was not proportional to CuGL doses, but enhanced after dosing of 0.05 mmol/kg and lowered by 0.10 mmol/kg. Like SGPT activity, serum urea nitrogen (SUN) concentration, an indicator of nephrotoxicity, significantly increased in proportion to doses of CuGL. Renal glutathione level was not different from control after dosing of 0.05 mmol/kg and lowered by 0.10 mmol/kg. In both organs, relative organ weight and lipid peroxide level were not affected by the treatment with CuGL; ascorbic acid level was elevated after dosing of 0.05 mmol/kg and was not different from control after treatment with 0.10 mmol/kg; like SGPT activity and SUN concentration, Cu level significantly increased in proportion to doses of CuGL. These results suggest that in the liver and kidney after the treatment with CuGL Cu accumulated may induce toxicity, leading to level changes of glutathione and ascorbic acid and to no induction of oxidative damage.

Selenium and glutathione peroxidase in human saliva and other human body fluids.

Human body fluids such as mixed saliva, erythrocyte, plasma and mature breast milk were analysed for selenium (Se) and Se-dependent glutathione peroxidase (GSH-Px), which is the only active form of Se known in man. Selenium-dependent GSH-Px activity was detected for the first time in human mixed saliva. Body fluid GSH-Px, Se and protein contents expressed in terms of volume increased in the order, saliva less than milk less than plasma less than erythrocyte. However, the sequence of increase for GSH-Px (U/mg protein) and GSH-Px-bound Se (%) was plasma less than milk less than erythrocyte less than saliva, and that for Se (ng/mg protein) was erythrocyte less than saliva less than plasma less than milk. Significant positive correlations were found between GSH-Px and Se contents and between protein and Se contents expressed per volume for human saliva, erythrocyte and the whole human fluids investigated. Positive correlations between erythrocyte and plasma Se (ng/mg protein) and between plasma and saliva GSH-Px-bound Se (%) were also significant.

Selenium in Japanese baby foods.

The selenium content of various baby foods was determined by spectrofluorimetry. Mean levels of Se (ng ml-1) decreased in the sequence: pasteurized cow's milk (28.4) greater than raw cow's milk (23.1) greater than mature human milk (22.5) greater than milk-based infant formulae (6.6). The sequence of mean values of Se (ng mg-1 protein) was: human milk (1.57) greater than raw cow's milk (0.96) greater than infant formulae (0.37). Dietary Se intake (microgram day-1) of 3 month old infants fed on infant formula and various milks decreased in the order: human milk (21.0) greater than pasteurized cow's milk (18.9) greater than raw cow's milk (15.0) greater than infant formulae (5.4). There was a significant positive correlation (r = 1.00, p less than 0.001) between the Se content of the infant formula product and that of the pasteurized milk product of three manufacturers. Hot air treatment reduced the Se content of cow's milk with increasing temperature and time of heating: loss of Se amounted to 11.1% at 210 degrees C for 25 min. The Se content of human milk was positively correlated (r = 0.64, p less than 0.001) with its protein content and negatively correlated (r = -0.77, p less than 0.01) with its fat content. These correlations were not found for infant formulae.

Sequential study on glutathione peroxidase and selenium contents of human milk.

Breast milk samples collected sequentially from five lactating women were analysed for selenium and Se-dependent glutathione peroxidase (GSH-Px), which is the only active form of Se known in man. Both GSH-Px and Se contents of breast milk decreased with increasing time of lactation and reached a plateau at a month post-partum. This sequential change was not due to the Se intake of the mother as reflected in urinary Se content. GSH-Px and Se contents of mature milk were strictly regulated irrespective of the Se intake of the mother. There was a significant positive correlation between GSH-Px and Se contents of breast milk. Mean GSH-Px and Se contents and the proportion of GSH-Px-bound Se content of the total Se content in mature milk were 38.8 U ml-1, 22.5 ng ml-1 and 23.4%, respectively. Preservation of mature milk at -20 degrees C decreased linearly its GSH-Px activity with increasing time at a rate of 5.8 U ml-1 day-1.