In this study, we attempted to identify significant baseline factors for the clinical efficacy and side effects of bromperidol (BPD) using multivariate analysis of variance (MANOVA).
Subjects for this study consisted of 61 psychiatric patients, almost all of whom were schizophrenic. BPD was administered to the patients for 6 weeks by a non-fixed open method (dose and duration not fixed).
Psychiatric symptoms and side effects were assessed using the Brief Psychiatric Rating Scale (BPRS) and UKU Side Effects Rating Scale at the time of initiation and after 6 weeks of the therapy. The background baseline characteristics of the patients were also evaluated: sex, age, height, weight, hereditary disposition of psychiatric disorders, diagnosis, duration of illness, number of recurrent episodes, acute exacerbation, responses to previous antipsychotics, daily dosage of BPD, concomitant antiparkinson drugs, and the plasma levels of BPD and prolactin.
For the statistical analysis, to identify these baseline factors closely associated with a good prognosis and/or side effects, a multivariate analysis of variance was applied, using the Statistical Analysis System (SAS).A higher improvement rate of BPRS total score was obtained in the group with good response to previous antipsychotics, low daily dosage, high plasma levels of BPD, and low initial score of “anergia”, and in those without an acute exacerbation (the chronic course).
The chronic course was associated with a significantly higher improvement rate of “hostile-suspiciousness”. Good response to previous antipsychotics was related to “anergia”, “thought-disturbance”, “activation” and “hostile-suspiciousness”. Low daily dosage was found to contribute to the improved “anxiety-depression”, “thought-disturbance”, “activation”. Higher plasma levels of BPD were related to “anxiety-depression”. A higher “anergia” subscale score was especially associated with the lower improvement rate of each subscale except “anxiety-depression” of BPRS. Regarding side effects, there were no identifiable factors contributable to side effects.
These methods of multivariate analysis seem to be quite useful in the field of clinical psychopharmacology for the analysis of the great volume of data consisting of qualitative and quantitative factors, and also to identify those factors contributing to the effcacy and side effects.

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The purpose of this study was to determine the relationships between the hemodynamic e ffects, plasma nitroglycerin (NTG) levels, and plasma cGMP levels with short-and longterm administration of NTG.
In the first part of the study, 20 patients with old myocardial infarction received increasing stepwise dosages of intravenous NTG ffom 0.05 to 05μg/kg/min. Coronary diameters were measured using coronary angiography and measurements were made on hemodynamic parameters as well as arterial and venous plasma NTG and cGMP levels.
In the second part of the study, 15 patients with congestive heart failure or unstable angina received intravenous NTG infusions at a constant rate for 24 hours. Hemodynamic parameters as well as arterial and venous plasma NTG and cGMP levels were measured repeatedly over this 24-hour period.
In the first part of the study, there was a significant arterialvenous plasma NTG concentration gradient and cGMP production (venousarterial plasma cGMP concentration gradient) was observed at the peripheral vascular bed during short-term NTG administration. Pulmonary arterial wedge pressure and mean aortic pressure dose-dependently decreased, and the epicardial coronary artery was dose-dependently dilated. Arterial plasma NTG levels were significantly correlated with percentage changes in hemodynamic parameters over short-term administration and this relationship was found to be independent of the venous plasma levels of NTG. Based on the above hemodynamic effects and the plasma concentration of NTG, the arterial plasma NTG level can be said to be a better index of NTG effects than the venous level.
In the second part of the study the systemic blood pressure and pulmonary arterial wedge pressure fell and remained significantly lower than the baseline values throughout the initial 6 hours, but did not differ significantly from the baseline at either 12 or 24 hours. The arterial-venous NTG concentration gradient was diminished at the 24-hour point to a level which differed significantly from the values at the 1-hour point. The production of cGMP also dminished.
These findings suggest that extensive uptake and/or metabolism of NTG by the peripheral vascular bed may occur in the non-tolerant state but not in the nitrate tolerant state.

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Serum transaminase (AST and ALT) values were monitored after administration of placebo to 104 healthy male volunteers for a phase I study. Both values remained within normal ranges in most of them. However, AST or ALT was above the normal range in 13 volunteers (12.5%). Their clinical features were ALT>AST, high serum γ-glutamyl trans peptidase, high serum triglyceride, high obesity index, or a combination of any of the four. We concluded that AST or ALT is likely elevated in volunteers showing these clinical signs; this should be noted in the evaluation of drug toxicity in future phase I studies.

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Malotilate, an agent used for the treatment of liver disease, is extensively metabolized; the pharmacokinetic profile of malotilate is ready altered in patients with liver diseases. The differences in pharmacokinetic profiles of malotilate between compensatory and noncompensatory liver cirrhosis patients were estimated. During repeat oral administrations of malotilate (200 mg three times daily for seven days), the plasma concentration of unchanged malotilate, M-1 and M-3 increased remarkably in the noncompensatory liver cirrhosis patients compared to that in the compensatory group.Plasma concentration of M-6 and urinary excretion of M-6 decreased with the impairment of liver functions; this was particularly true of in non compensatory liver cirrhosis patients.

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The purpose of this study was to investigate the effects of various beta-blockers on blood pressure (BP) and pulse rate (PR) profiles of 77 patients with essential hypertension (49 men and 28 women aged 56±16 years) and 86 normotensive individuals (controls).
The drugs tested were atenolol (50 mg), nipradilol (6 mg), metoprolol (80 mg), and pindolol (10 mg). Each drug was randomly administered to a subgroup of essential hypertensives twice a day. BP and PR were noninvasively measured at 30-min intervals for 24 hours using an ABPM-630 (Nippon Colin Ltd.) before and 4 weeks after the start of treatment. The effects of each drug on the level (MESOR) and the pattern (amplitude and acrophase) of diurnal variations in the periodic regression curve, which fitted data to a periodicity of 24 and 12 hours, were investigated using periodic analysis of covariance.
There was no significant difference in BP or PR levels between all groups before treatment. The mean 24-hour systolic blood pressure (SBP), diastolic blood pressure (DBP), and PR were significantly (p<0.01) reduced after treatment in each group; there was no significant difference in the degree of SBP reduction between the hypertensive groups. DBP reduction was significantly (p<0.01) greater in the nipradilol group (-13 mmHg) than in the pindolol group (-5 mmHg), but no significant difference was found between the atenolol or metoprolol groups and the other 3 groups. There was a significant (p<0.01) change in PR levels after treatment between the atenolol group (-8 bpm) and the metoprolol (-3bpm) or pindolol groups (-4 bpm).
The diurnal BP or PR patterns of all groups before treatment were basically the same as those of the normal controls. The diurnal post-treatment pattern of the atenolol and nipradilol groups remained the same as that of the normal controls, but that of the meto-prolol and pindolol groups was significantly (p<0.05) different compared with the controls. The reason for this was that atenolol and nipradilol caused proportional daytime and nighttime reductions, while metoprolol had little effect on the morning BP and pindolol had a lesser effect during sleep.Metoprolol is relatively short acting and pindolol has intrinsic sympathetic activity.
Thus, different beta-blockers have specific hypotensive or depressive effects on the BP and PR profiles; these characteristics seem important to consider in the treatment protocol of individual hypertensive patients.

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The cardiac electrophysiological effects of pentisomide, a new class I antiarrhythmicagent, were studied in 14 patients with sunraventricular tachycardia.
Pentisomide did not significantly change sinus cycle length, PA time, and AH and HVintervals at 1.5 hr after a single oral administration of 300, 400 or 600 mg. Furthermore, theantegrade and retrograde refractory periods of AV node and the accessory pathway were notsignificantly changed. However induction of supraventricular tachycardia was suppressed in 5out of 14 patients. Three of the 5 patients showed AV nodal reentrant tachycardia (AVNRT), 1 intra-atrial reentrant tachycardia (IART) and 1 concealed Wolff-Parkinson-White (WPW) syndrome. Pentisomide blocked the retrograde conduction in AV node in 3 patients with.AVNRT. The retrograde conduction in the accessory pathway was blocked in the patientwith concealed WPW syndrome. The plasma concentration of pentisomide at 1.5 hr afteradministration was 3.0±1.5 μg/ml in the effective cases and 2 .3±1.5 μg/ml in ineffectivecases (no statistically significance).
Conclusion: A single oral administration of pentisomide showed no statistically significantinfluence on the electrophysiological parameters of human hearts, whereas it was effective insuppression of supraventricular tachycardia by the mechanism of retrograde conduction blockin several patients.

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