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Articles by K. Sawada
Total Records ( 2 ) for K. Sawada
  M Miura , N Takahashi , M Nara , N Fujishima , H Kagaya , Y Kameoka , H Saitoh , H Tagawa and K. Sawada

A steady-state trough plasma itraconazole concentration greater than 500 ng/mL is a therapeutic target for itraconazole. A simple, rapid and sensitive high-performance liquid chromatography-based method was developed for quantitation of itraconazole and hydroxyitraconazole in human plasma.


Itraconazole and hydroxyitraconazole were separated using a mobile phase of 0.5% KH2PO4 (pH 6.0)-acetonitrile (30:70, v/v) on a CAPCELLPAK C18 MGII column at a flow rate of 0.5 mL/min and ultraviolet absorbance at 260 nm.


The analysis required 200 µL of plasma and involved a rapid, simple solid-phase extraction with an Oasis HLB cartridge, which resulted in recoveries of 87–92% for itraconazole and 91–94% for hydroxyitraconazole. The lower limit of quantification for itraconazole and hydroxyitraconazole was 5 ng/mL each. Intra- and interday coefficients of variation for itraconazole and hydroxyitraconazole were less than 11.3% and 12.2%, respectively, and accuracies were within 11.7% and 4.5% over the linear range, respectively. Although the steady-state plasma concentrations of itraconazole and hydroxyitraconazole ranged from 506 to 2482 ng/mL and from 766 to 2444 ng/mL, respectively, after a two-day loading dose of 400 mg/day intravenous itraconazole followed by the administration of 200 mg/day itraconazole oral solution, calibration curves of itraconazole and hydroxyitraconazole showed positive linearity in a concentration range of 5–2500 and 50–2500 ng/mL, respectively.


Our results indicate that this method is applicable for the monitoring of plasma levels of itraconazole and hydroxyitraconazole in a clinical setting. Furthermore, the regimen presented here might also be effective in preventing infection, but further studies with large sample sizes are necessary to investigate this avenue.

  K. Sawada , K. Nagano and N. Nishino
  In this study, plasma 3-Methylhistidine (3-MH) and other Amino Acids (AA) were measured in high yielding dairy cows between 1 week prepartum and 4 weeks postpartum to evaluate the effect of different protein levels in a postpartum diet on milk performance, metabolites and feed intake. Eleven multiparous cows were used in the study and all received the same prepartum diet. Postpartum, they were divided into two groups; five cows received a diet of 19% CP (CP19) and six cows received a diet of 17% CP (CP17). Plasma 3-MH and also other AA concentrations were significantly lower in the CP19 cows than in the CP17 cows. The peak plasma 3-MH concentration postpartum in CP17 and CP19 were 15.5 and 9.9 μM, respectively while the mean plasma 3-MH concentration throughout the trial in CP17 and CP19 were 11.7 and 7.6 μM, respectively. Milk yield and composition tended to improve in CP19 cows, however, these were not significant. Blood Urea Nitrogen (BUN) was significantly higher in CP19 than that in CP17 (14.3 vs. 9.9 mg dL-1, respectively). The kinetics of plasma 3-MH were the same as a earlier study where it increased after parturition for 1 week and then progressively decreased until 4 weeks postpartum. These results indicate that muscle protein mobilization can be lowered by protein in the diet as evidenced by plasma 3-MH. Lower AA might be an indication of their efficient utilization from the diet, so that an increased consumption of AA for milk production is reflected in lower AA levels in blood. This study suggested that even for cows receiving 19% CP in early lactation, if the AA utilization into milk protein is efficient, BUN can be kept within a normal range. In conclusion, plasma 3-MH is a sensitive and useful index for protein nutrition in early lactation and a 19% CP diet might be effective in preventing body protein degradation as evidenced by plasma 3-MH.
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