Mizoribine is an orally available immunosuppressive agent, which has been on the market since 1984 in Japan for the prevention of rejection in renal transplantation.1) In contrast to other immunosuppressive agents (e.g., azathioprine), mizoribine has been shown in animal experiments to lack oncogenicity and has shown clinically a low incidence of severe adverse drug reactions (such as myelosuppression and hepatotoxicity), making it useful in long-term immunosuppressive therapy.2) After oral administration, mizoribine is absorbed rapidly from the gastro-intestinal tract and distributed into living cells according to a concentration gradient between the extracellular and intracellular environment. It is completely eliminated from blood circulation within 24 h, and is excreted in urine (85%), feces (9.7%), and bile (Ͻ1%). 1,3) As elimination rate of mizoribine is highly dependent on renal function, low-dose mizoribine (1 to 3 mg/kg/d) was administered to patients whose renal function did not return soon after transplantation. However, renal function returns much earlier following transplantation due to the concomitant use of calcineurin inhibitors. High-dose mizoribine (5 mg/kg/d) has been administered since 1998 to a number of patients, and has been shown to be safe and well tolerated in renal transplant patients at doses up to 5 mg/kg/d. 4,5) In addition, Akiyama et al. reported that patients treated with Ն5 mg/kg/d of mizoribine showed about 20% fewer acute rejection episodes at 3 months post-transplantation than those with Ͻ5 mg/kg/d of mizoribine.4) Recently, phase 1 single-and multiple-dose studies have been carried out to confirm the safety, tolerability, and pharmacokinetics of higher-dose (up to 12 mg/kg/d) mizoribine.5) In the phase 1 study, no notable or clinically relevant abnormality was observed in the clinical laboratory values except for transient elevation in serum uric acid at the highest dose level (multiple dose of 12 mg/kg/d). 5)In the present study, to evaluate the pharmacokinetic characteristics of mizoribine in subjects with normal renal function, we estimated the population pharmacokinetic parameters of mizoribine using a nonlinear mixed effects model (NONMEM) program.6) Pharmacokinetic data for population analysis were obtained in the previous phase 1 study, where 24 healthy Caucasian male subjects participated in a singledose (3, 6, 9, 12 mg/kg) study, and 12 subjects participated in a multiple-dose (6, 12 mg/kg/d) study.5) In addition, to assess linearity and constancy in the pharmacokinetics of mizoribine, the pharmacokinetic parameters in individual 36 subjects were obtained from the population estimates according to Bayes' theorem using the NONMEM post-hoc option.6) We further evaluated the precision of Bayesian analysis in the sparse sampling protocol by using pharmacokinetic data obtained from 24 subjects in the single-dose study. 5) MATERIALS AND METHODSPharmacokinetic Data Serum mizoribine concentration data for population pharmacokinetic analysis were obtained in the previous stu...

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The aim of this study was to develop a comprehensive analytical method for the characterisation of stevia sweeteners in soft drinks. By using LC and time-of-flight MS, we detected 30 steviol glycosides from nine stevia sweeteners. The mass spectral data of these compounds were applied to the analysis to determine steviol glycosides in nine soft drinks. On the basis of chromatographic data and principal-component analysis, these soft drinks were classified into three groups, and the soft drinks of each group, respectively, contained high-rebaudioside A extract, normal stevia extract or alfa-glucosyltransferase-treated stevia extract.

Sporeamicin A is a new erythromycin-type antibiotic isolated from a species of Saccharopolyspora. It was active in vitro against a wide variety of Gram-positive bacteria. In vitro studies indicated that the sporeamicin A was stable in the presence of human serum, although it was bound to serum proteins. Sporeamicin A was effective in the mouse protection test against Staphylococcus aureus, Streptococcuspyogenes and Streptococcuspneumoniae. Sporeamicin A attained higher plasma and tissue levels in the rat than did erythromycin stearate.