We investigated adenylate cyclaserelated hormone actions induced by colforsin daropate hydrochloride (Adehl^® Inj.: AD) injected by intravenous administration at 0.5 μg/kg/min for 3 hrs in 9 male healthy volunteers (age;21-32 y), compared with control administration of physiologic saline. Adenylate cyclaserelated parameters on serum chemistry, urine test and hormone secretion levels were measured at preadministration and, 1 and 3 hours after administration. [Statistics] As for statistic analysis to determine agent effects, we adopted both 95% confidence interval test (95%CI-test) and paired t-test. By 95%CI-test, we detected the discrepancy between 95% CI of each observed data and its standard value range, and by paired t-test we detected data changes between preadministration and post-administration. [Results] Adrenaline, insulin, ACTH, cortisol, NEFA, glycerol, and FT₃, increased among glucose metabolism-or fat metabolism-related parameters. Concerning bone/Ca metabolism-related parameters, serum Ca, ALP, totalprotein, albumin, and serum cAMP increased while serum P and PTH-I decreased. And serum K decreased in water absorption-related parameters of kidney function. In sex hormones, FSH and testosterone in-creased. In the other hormones, noradrenaline and plasma renin activity increased. However, changes of all the detected parameters were transient within their normal ranges or standard limits, and were graded in minute or slight (plasma rennin activity only). [Discussion & Conclusion] We concluded that almost all the changes of these observed parameters were attributed to AD hemodynamic effects such as chronotropic action, inotropic action and vasodilating action, which were linked to hormonal secretion level changes (ACTH increase, adrenaline increase, noradrenaline increase) by way of cardiovascular homeostasismechanism or auto-regulation system. Concerning the slight increase of serum cAMP, it had no linkage to any hormonal secretions. The PTH-like action of AD such as PTH-I decrease reported in the precedent animal study was also observed.

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A prospective post-marketing surveillance study of amrinone (Amcoral^® injection 50 and 100) was carried out for one year from April 2000 until March 2001 in patients with acute cardiac failure (including acute exacerbation of chronic cardiac failure) inadequately controlled with other drugs in the field of internal medicine in order to identify the influence of the drug on platelet count. The results were as follows:
1. One hundred and ninety-nine cases (safety evaluable population: 198 ; efficacy evaluable population: 191) collected from 37 medical institutions were evaluated.
2. Efficacy rate in overall improvement rating was 72.1%, which was higher than that reported in the reexamination (65.9%).
3. Adverse drug reactions were reported in 32 (16.2%) patients. Of these, 18 (9.1%) patients had thrombocytopenia.
4. Fourteen of 18 patients with thrombocytopenia were elderly patients (≥75 years), indicating that this adverse drug reaction occurs more frequently in elderly patients and patients treated with drugs against cardiac failure just before the start of treatment with amrinone.
5. The majority of patients who had thrombocytopenia after treatment with amrinone exhibited increased CRP, a parameter of inflammation, suggesting that CRP is likely to be a predictor of the development of thrombocytopenia.
6. The other adverse drug reactions observed were decreased blood pressure (6 patients, 3.0%), arrhythmia (6 patients, 3.0%), anemia (2 patients, 1.0%), and aggravated hepatic function (1 patient, 0.5%).

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Objective: Lowering blood pressure (BP), and improving lipid and glucose metabolism are the most important factors in preventing cardiovascular events in hypertensive patients with dyslipidemia. This study was conducted to investigate the effects of long-term combination therapy with an ACE inhibitor, captopril, and an HMG-CoA reductase inhibitor, pravastatin, on hemodynamics, and lipid and glucose metabolism in hypertensives with hypercholesterolemia.
Methods: After a 2-month (M) placebo-run-in period, hypertensive patients with hypercholesterolemia (total cholesterol [TC]>6.21mmol/L) were recruited for the study. They were treated with captopril for 6 M, and then pravastatin was added for the following 18 M. BP and serum lipid and fasting plasma glucose (FPG) were determined during the periods of placebo-run-in, captopril monotherapy, and the combination therapy.
Results: Two of 24 participants dropped out from the study. Thus, data were analyzed in 22 participants, and 11 of them had glucose intolerance. Both systolic and diastolic BP were significantly reduced from 169.0/100.9 mmHg to 145.5/83.8 mmHg without changes in heart rate by captopril monotherapy, and those effects were maintained during the combination therapy. After 18 M of the combination therapy, serum lipid levels were significantly reduced by 13.9% in TC (baseline 6.67mmol/L), 13.9% in triglycerides (2.15mmol/L), and 19.9% in LDL-C (4.47mmol/L), while HDL-C was increased from 1.11 to 1.29mmol/L. FPG and HbA_1c levels were significantly reduced from 6.08 to 5.47mmol/L and 6.8 to 6.2%.
Conclusion: These results suggest that long-term combination therapy with captopril and pravastatin is beneficial for hypertensive patients with hyperlipidemia regardless of whether they have glucose intolerance.

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[in Japanese]

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