Interindividual differences in the clinical effects of 5-HT(3) receptor antagonists could be evaluated based on receptor occupancy theory, and the differences varied among drugs. Drug selection considering these individual variations might be useful for the patients who experienced vomiting associated with chemotherapy.

We developed a novel method for measuring glycated (glc) proteins in biological samples, based on the colorimetry of 2-keto-glucose which is released from the glc protein (ketoamine) on heating with hydrazine. The ketoamine-induced coloration remained constant at room temperature (25-27 degrees C) for 1 h. The method gave reliable precision and accuracy. However, high concentrations of serum pigments caused positive interference, suggesting that hemolytic or hyperbilirubinemic serum would give false-positive results. The concentration of glc protein in clinical serum samples measured by the present method (y) correlated well with those (fructosamine values, x) measured by the nitroblue tetrazolium-reducing method: y = 1.27x-1.69 (r = 0.92, n = 93). The concentrations (microM, mean +/- S.D.) of glc protein in sera from normal and diabetic subjects were 275 +/- 37 (n = 32) and 403 +/- 98 (n = 32), respectively, and the concentrations (nmol/mg hair, mean +/- S.D.) of glc protein in back hairs from non-diabetic and diabetic rats were 3.7 +/- 0.3 (n = 10) and 8.6 +/- 1.5 (n = 10), respectively. Thus, the technique gave reasonable concentrations of glc proteins in humans and rats with diabetes mellitus, indicating it to be reliable and diagnostically useful.

To evaluate the antiemetic eŠects of 5-HT 3 receptor antagonists, we investigated the relationship between condition of food intake and occurrence of nausea and vomiting. We collected data such as sex, age, disease, combination of steroids and central antiemetic agents, eating condition, and vomiting condition from medical records in 33 hematologic cancer patients receiving chemotherapy; combination with 5-HT 3 receptor antagonists. The conditions of food intake and nausea/vomiting were checked at 4 mealtime points (lunch, supper, breakfast, and next lunch) after chemotherapy, and were recorded as 1, 3, or 5 as each condition score. To calculate eating scores and nausea/vomiting scores, the sum of scores from 4 mealtime points was used. We found a signiˆcant negative correlation between eating scores and nausea/ vomiting scores (n＝62, p＜0.01). At eating points in which combination therapy with steroids and central antiemetic agents was not given, antiemetic eŠects of granisetron, azasetron and ramosetron were compared and revealed that azaseton was the most eŠective antiemetic agent. This result is inagreement with our previous study predicting antiemetic eŠects of 5-HT 3 receptor antagonists based on the receptor occupancy theory. This study suggests that eithes receptor occupancy or eating score is a useful indicator for assessment of the e‹cacy of 5-HT 3 receptor antagonists.

We tried to measure glycated proteins by a novel method based on colorimetry of 2-keto-glucose which is released from the glycated protein (ketoamine) on heating with hydrazine. Reaction conditions were optimized with glycated human serum albumin (glc HSA) as a model compound. Ketoamine reacted quantitatively with hydrazine on heating at 100 degrees C for 0.5 h, followed by heating with phenylhydrazine at 60 degrees C for 1 h. Glucose interference with the assay was eliminated by preincubation of the sample with glucose oxidase at 37 degrees C for 0.5 h. Time courses for the coloration of glc HSA and human serum showed a profile similar to that of N-p-tolyl-D-isoglucosamine under optimized reaction conditions. The lower limit for the assay of glc HSA was 0.7 microM. The serum level of glycated proteins measured by the present method correlated well with that (fructoamine value, microM) measured by the conventional method (nitroblue tetrazolium-reducing method) (r = 0.92, n = 35). In conclusion, the present method is a novel, highly sensitive and reliable one for measuring glycated proteins in biological samples.

5-HT(3) receptor antagonists are widely used as antiemetic agents in clinical setting, of which palonosetron, with a long elimination half life (t(1/2)), has recently become available. It is important to evaluate the concentration of serotonin when investigating the antiemetic effects of 5-HT(3) receptor antagonists, as those effects are not based solely on the t(1/2) value. We theoretically evaluated the antiemetic effects of three 5-HT(3) receptor antagonists (granisetron, azasetron, palonosetron) on cisplatin-induced nausea and vomiting by estimating the time course of the 5-HT(3) receptor occupancy of serotonin. We estimated the 5-HT(3) receptor occupancy of serotonin in the small intestine, based on the time course of plasma concentration of each 5-HT(3) receptor antagonist and the time course of concentration of serotonin near the 5-HT(3) receptor in the small intestine after administration of cisplatin. The antiemetic effect of each 5-HT(3) receptor antagonist was evaluated based on the normal level of 5-HT(3) receptor occupancy of serotonin. Our results suggest that an adequate antiemetic effect will be provided when a dose of 75 mg/m(2) of cisplatin is given to patients along with any single administration of granisetron, azasetron, or palonosetron at a usual dose. On the other hand, the 5-HT(3) receptor occupancy of serotonin was found to be significantly lower than normal for several days after administration of palonosetron, as compared to granisetron and azasetron, indicating that constipation may be induced. Our results show that granisetron, azasetron, and palonosetron each have an adequate antiemetic effect after administration of 75 mg/m(2) of cisplatin.