Effect of low-dose ranitidine on gastric pH after stimulation of gastric fluid secretion was evaluated using 4μg/kg of intramuscularly administered tetragastrin (TG) in 12 healthy male volunteers. The study was a randomized, placebo-controlled, four-way, cross-over trial. A wash-out period of 1-week was maintained between each treatment. Treatment administration was as follows: (1) 14.06 mg (hereafter 14mg) ranitidine, TG at t=1hr.(2) 28.13 mg (hereafter 28mg) ranitidine, TG at t=1hr.(3) 56.25mg (hereafter 56mg) ranitidine, TG at t=1hr.(4) Placebo, TG at t=1hr. Gastric pH was continuously monitored for 6 hours through a micro-pH-electrode in every subject. Gastric fluid acidity was measured at t=0, 1, 2, 3, 4 and 5 hr after ranitidine administration. Average gastric pH values for 6 hours were increased by ranitidine treatment from 2.08±0.48 (placebo) to 3.60±1.10 (14 mg, p<0.05 vs placebo), to 3.83±1.41 (28mg, p<0.05 vs placebo), and to 4.76±1.50 (56 mg, p<0.05 vs placebo, 14mg, 28mg).
A dose-related increase in pH holding time was also observed. Gastric acidity was increased with TG in the placebo group from 53.1±27.6mEq/L (t=1hr) to maximum 120.8±31.8mEq/L (t=2hr) and returned to baseline value at t=5hr. Ranitidine treatment significantly suppressed the increase in gastric acidity in a dose-related manner (t=2hr: 14mg, 103.9±18.0 mEq/L: 28mg, 98.9±25.6mEq/L: 56mg, 77.1±36.5mEq/L). The results indicated that low-dose ranitidine inhibited the secretion of gastric fluid induced by TG administration and increased gastric pH in a dose-related manner.

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We performed a pharmacoepidemiological study on triazolam dependence with typical doses in out-patients of Fukui Medical School Hospital. We investigated the prescriptions (duration of treatment and total dose prescribed) for patients administered triazolam.
The patients were classified according to the prescription pattern of this drug, Group 1: patients who had been prescribed triazolam daily, Group 2: those who had been allowed to take triazolam when they cannot sleep.Approximately 40% of all the patients had been prescribed triazolam for 8 months or longer, and were judged to be normal dose dependence. The prevalence of this dependence was apparently higher in group 1 than in group 2.

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For use as reference individuals, the clinical laboratory data of young healthy males was analyzed at the screening examination for a phase I study (n=204-2278) and also during placebo administration (n=58-141).The conclusions are as follows:
1. Normality of the distribution pattern was not proven in 26 items out of 50 items at the screening examination. The other 24 items were proved to be of normality. The natural logarithm conversion most frequently gave the normal distribution pattern.
2. The rejection rate of the twice rejection procedure for 2SD was between 6-10%, and that for 3SD was less than 4% in most subjects.
3. The reference limits were coincidential between the data calculated by three parametolic methods (original data, square root and natural logarithm) and non-parametolic method independent of the distribution pattern, when the values calculated by these three methods were nearly equal.
4. Significant circadian rhythm was observed in 8 items of the 15 clinical hematology data and in 16 items of the 26 biochemical data during the placebo adiministration period. A significant variation of greater than 5% was observed in 9 items: white blood cell, neutrocyte (%), lymphocyte (%), eosinophil cell, triglyceride, total-bilirubin, CPK, amylase and inorganic phosphate.

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We investigated the serum digoxin concentration (SDC) by TDx Digoxin II assay in 113 elderly patients who were not receiving any cardiac glycosides. Most of the falsely elevated SDCs were regarded as negligible clinically, whereas some of the values were markedly high. It was of interest that all of four false positive SDCs exceeding 0.3 ng/ml were derived from patients undergoing continuous intravenous drip infusion with sodium containing solution at the time of sampling.
In conclusion, TDx Digoxin II may be applicable to the elderly who are not receiv ing intravenous sodium infusion treatment. However, since false positive SDC can become elevated in aged patients undergoing this therapy, careful attention must be paid to such patients.

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We present a convenient reference to predict the appropriate daily dosages (D) of beta-methyldigoxin (BMD) from serum creatinine, serum albumin (Alb), and body weight in elderly patients. In this study, the clinical utility of the reference was compared with that of the previously proposed method to predict D from only estimated creatinine clearance (CL_cr). In addition, relative contributions of Alb and CL_cr to total glycoside clearance at steady state (CL_tot) were assessed to ascertain the indispensability of Alb as the predictor. A total of 61 inpatients aged 70 years and over were prospectively studied. The present method provided a closer correlation between the serum glycoside concentration and the ratio of actual to predicted D (r=0.652) than the previously proposed method (r=0.567). In addition, multiple regression analysis revealed that both of Alb and CL_cr contributed to explain the variance in CL_tot with similar significance (Alb: F-value=18.64, p=0.0001, CL_cr: F-value=16.67, p=0.0001). We consequently concluded that this simple reference is more preferable to the previous method because of its accuracy and convenience in use, and that Alb is necessary for predicting D in the elderly.

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