Transdermal monotherapy with mepindolol BIO TSD in patients with stable angina pectoris. Placebo-controlled, crossover investigation of a new therapeutic concept with 12-hours overnight application.

10 patients (6 females and 4 males with an average age of 75 years) with stable angina pectoris were treated transdermally with mepindolol in a balanced, randomized, controlled, crossover study to compare the anti-ischemic effects of 12-hour overnight, and 24-hour applications. The number of angina pectoris attacks, the oral nitrate consumption and the ischemic parameters in 24-hour ECG, i.e. episodes of manifest (MMI) and silent (SMI) myocardial ischemia, the total duration of ischemia and 24-hour heart rate profiles were investigated. Both application schemes showed typical systemic beta blocker effects in all patients and significant clinical efficacy. A dose/effect relationship and a time/effect relationship between the two different application schemes were demonstrated across all the parameters investigated. Systemic and local tolerance of the therapy was good. 2 patients showed transient, mild skin irritation, but only during one phase of the study. Premature discontinuation was not necessary in any cases. There were no relevant changes in the clinical-chemistry. The new therapeutic concept of 24-hour treatment for a. pectoris with 12-hour overnight transdermal applications showed both good clinical efficacy and a good safety profile.

[Anti-ischemic action of the transdermally-applied beta-receptor blocker, mepindolol, in patients with stable angina pectoris. Comparison with transdermal nitrate]. / Antiischämische Wirkung des transdermal applizierten beta-Rezeptorenblockers Mepindolol bei Patienten mit stabiler Angina pectoris. Vergleichsstudie mit transdermalem Nitrat.

A new transdermal beta-blocker containing system (Mepindolol BIO TSD) was compared in a placebo controlled cross over trial with a transdermal nitrate system in 14 patients suffering from coronary heart disease with stable angina pectoris. Under Mepindolol TSD both the incidence of angina pectoris attacks and the consumption of oral nitroglycerin dropped significantly. Under ergometry it resulted in an improvement in the maximum exercise tolerance and in a significant reduction in the ischemic ST-Segment deviation. Under Holter monitoring the number of manifest (MMI) and silent (SMI) ischemic episodes was significantly reduced. In addition the total duration of ischemia was significantly reduced. All the examined parameters showed Mepindolol BIO TSD to be significantly more effective than transdermal nitrate, and the duration of action was longer. No clinically relevant adverse events were observed in any of the therapeutic regimes.

[Anti-ischemic action of the transdermally applied beta-receptor blocker, mepindolol in patients with stable angina pectoris]. / Antiischämische Wirkung des transdermal applizierten beta-Rezeptorenblockers Mepindolol bei Patienten mit stabiler Angina pectoris.

A new transdermal system (BIO TSD) containing the beta-adrenergic blocker mepindolol was assessed in a placebo controlled clinical trial in 12 patients with coronary heart disease. On therapy, the number of anginal attacks and the consumption of oral nitroglycerin (glyceryl trinitrate) were reduced significantly. During ergometer exercise the exercise tolerance was improved and the ischemic ST-segment depression was reduced significantly. Holter monitoring revealed significant reductions of the number of manifest and silent episodes and the total duration of ischemia. No relevant side effects were observed.

The bioavailability of methylepoxyproscillaridin (P35): a new semisynthetic cardiac glycoside.

The pharmacokinetic data of methylepoxyproscillaridin (3'-methyl-4'-5'-epoxyproscillaridin) (P35) after 1 mg i.v. or oral administration in two different galenic preparations (hard and soft gelatin capsules) in randomized succession were studied in 9 healthy volunteers, showing a bioavailability of 88 +/- 10.5% (soft gelatin capsule) and 81 +/- 12% (hard gelatin capsule). The half-life of P35 was calculated to be 80 +/- 13.3 h.

Hemodynamic effect of methylepoxyproscillaridin (P35) in patients with congestive myocardiopathy.

The hemodynamic effect of methylepoxyproscillaridin (3'-methyl-4'-5'-epoxy-proscillaridin) (P35) was studied according to the Swan Ganz thermodilution method in 6 patients with latent cardiac insufficiency. Both at rest and under ergometer exercise, the stroke volume and the systolic blood pressures increased under P35. Moreover, under physical exercise the heart rate decreased significantly, while cardiac output increased. The hemodynamic effect of P35 can therefore be regarded as typical of cardiac glycosides.