Comparison of the efficacy and safety of nifedipine coat-core versus amlodipine in the treatment of patients with mild-to-moderate essential hypertension. Hypertension Study Group.

The antihypertensive efficacy and safety of once-daily nifedipine coat-core was compared with that of once-daily amlodipine in a multicenter, prospective, double-blind, randomized, parallel-group study in which titration was based on response. The study consisted of a 2-week, single-blind, placebo run-in period followed by an 8-week double-blind treatment period. Double-blind treatment began with nifedipine coat-core 30 mg or amlodipine 5 mg. After 4 weeks of double-blind therapy, patients with a trough seated diastolic blood pressure (DBP) > or = 90 mm Hg received an increased dose of nifedipine coat-core (60 mg) or amlodipine (10 mg). A total of 207 patients received the study medication at 12 private-practice medical centers. Ambulatory blood pressure monitoring (ABPM) was performed at six medical centers with 38 nifedipine coat-core and 37 amlodipine patients. Data from 176 patients were valid for the primary efficacy analysis. Treatment groups were well matched with respect to baseline demographic and disease characteristics. During the study period, 59 (65.6%) nifedipine coat-core patients remained on their original 30-mg dose of study medication compared with 52 (60.5%) amlodipine patients who remained on the 5-mg starting dose. Mean trough blood pressure at baseline was 160.9/101.9 mm Hg in the nifedipine coat-core patients compared with 160.5/101.8 mm Hg in the amlodipine patients. Mean trough blood pressures at end point were 141.3/85.5 mm Hg and 140.7/85.9 mm Hg in the nifedipine coat-core and amlodipine groups, respectively. Equivalence between the two treatment groups was demonstrated based on the difference between amlodipine and nifedipine coat-core in the change from baseline in trough seated DBP (90% confidence interval, -0.50 to 2.59). Systolic blood pressure and 24-hour ABPM data supported the equivalent antihypertensive efficacy of the two treatments. Both drugs were well tolerated and had similar safety profiles. Nineteen patients in the amlodipine group experienced at least one adverse event compared with 12 in the nifedipine coat-core group. The amlodipine patients tended toward a later occurrence of adverse events plus a greater number of events, particularly edema and gastrointestinal symptoms. More patients in the nifedipine coat-core group (n = 3) than in the amlodipine group (n = 1) discontinued treatment because of adverse events.(ABSTRACT TRUNCATED AT 400 WORDS)

[Nisoldipine in stable angina pectoris. Efficacy and tolerance in comparison with diltiazem]. / Nisoldipin bei stabiler Angina pectoris. Wirksamkeit und Verträglichkeit im Vergleich zu Diltiazem.

Following a one-week placebo-controlled washout phase, 24 patients with stable angina pectoris (ST segment depression under ergometric exercise greater than or equal to 0.2 mV) were monitored and randomized to three months treatment with 1 x 10 mg nisoldipine/day or 3 x 60 mg diltiazem/day. Ergometries were performed 2 hours after administration of the first medication, and after 6 weeks and 3 months of treatment. Other parameters were the weekly incidence of angina pectoris attacks, and nitrate consumption, as well as laboratory tests prior to and at the end of treatment. Resting blood pressure and heart rate were only marginally influenced by both medications. The rate-pressure product at maximum ergometric load decreased by about 6% under both nisoldipine and diltiazem. The ST segment depression at maximum work load decreased under nisoldipine by approximately 75% (from 0.27 to 0.07 mV), and under diltiazem by about 55% (from 0.28 to 0.13 mV; p less than or equal to 0.01). In the nisoldipine and diltiazem groups, the number of weekly angina pectoris attacks decreased from an initial 3.4 and 3.3, respectively, to 0.16 and 1.0, respectively, after 6 weeks, and 0.14 and 0.9, respectively, after 3 months' treatment (p less than or equal to 0.01). The weekly consumption of nitrate decreased accordingly. The present data show that, in particular during long-term treatment of angina pectoris, the once-daily dose of 10 mg nisoldipine is superior to diltiazem 3 x 60 mg/day.

Low-dose nitrendipine in mild hypertension: a double-blind, placebo-controlled, comparative study.

The objective of this study was to determine whether 10 mg of nitrendipine once daily is adequate for treatment of mild hypertension. The study was a randomized, double-blind, multicenter, and placebo-controlled group comparison over 8 weeks (a 2-week placebo-controlled washout phase followed by a 6-week treatment phase) with measurement of blood pressure, routine laboratory tests, compliance monitoring, and recording of side effects every 2 weeks. The study subjects were 141 outpatients with mild arterial hypertension and were given one 10-mg tablet of nitrendipine or placebo once daily. The end point used was reduction in diastolic blood pressure (DBP) by at least 10 mm Hg or to less than or equal to 90 mm Hg; the responder rate at the end of the treatment phase was determined. After 6 weeks of treatment, the mean reduction in DBP was 11.8 mm Hg under nitrendipine compared with 5 mm Hg under placebo. The responder rates were 73% (53 of 73 patients) in the nitrendipine group and 26% (18 of 68 patients) in the placebo group. This difference is statistically significant. Side effects were reported by a total of 14 patients (6 in the nitrendipine group, 8 in the placebo group). There was one dropout in each group. No changes in laboratory parameters were observed. In conclusion, nitrendipine is suitable for monotherapy of mild arterial hypertension in the dosage of 10 mg once daily used in this study.

Preparative-scale enzyme-catalyzed peptide synthesis using solubilizing N-terminal protecting groups.

Several amino acid derivatives with the negatively charged N alpha-protecting groups Maleyl (Mal) and Citraconyl (Cit) were synthesized and used in enzyme-catalyzed peptide synthesis. Compared to commonly used alpha-amino protecting groups in chemical peptide synthesis (Z, Fmoc, Boc, etc.), these charged protecting groups strongly increase both water solubility of different aromatic amino acid derivatives and activities of synthesis reactions. As a consequence of the solubilizing effect, we used these groups in the kinetically controlled peptide synthesis choosing kyotorphin (tyrosyl-arginine) as a model peptide. With Mal-Tyr-OEt as substrate and Arg-OEt as nucleophile, we succeeded in the alpha-chymotrypsin-catalyzed production of about 12 kg of Tyr-Arg (50.4% overall yield) in a 300 l batch experiment.

Relationship between the venoconstrictor activity of dihydroergotamine and its pharmacokinetics during acute and chronic oral dosing.

In a double-blind, interindividual comparative study 30 healthy volunteers were randomly allocated to oral treatment with 5 or 10 mg of dihydroergotamine (DHE) or placebo once daily for 16 days. Regional basic venous blood volume (BBV), pressure dependent venous capacitance (CV) of the calf, resting heart rate and blood pressure were determined on Days 1 and 15 of treatment. Plasma concentrations of DHE were monitored on Days 2 and 16. Due to spontaneous vasodilation BBV varied considerably, showing that it is an inappropriate parameter for investigating the venoconstrictor activity of DHE. CV remained unchanged after the first dose of DHE but it had declined significantly on both dosage regimens at the end of the treatment phase. In contrast, the blood concentration profiles of DHE were comparable at the beginning and the end of the trial. The discrepancy can best be explained by the existence of an effect compartment, e.g. smooth vascular musculature, which slowly becomes filled with DHE and/or its active metabolites. The venoconstrictor activity of DHE exhibited a significant dose-response relationship.

Human diploid lung fibroblast cell lines WI 26 and WI 38 exhibit isozyme shift of alkaline phosphatase after viral transformation.

The testing of the type of membrane associated alkaline phosphatase (EC 3.1.3.1) by immunotitration has revealed that there is a shift from a liver-like type of alkaline phosphatase in normal cell cultures of the human diploid fibroblast cell strains WI 26 and WI 38 to a placenta-like variant in cultures of the same cell strains after the transformation by the DNA-tumor virus SV 40, the WI 26 SV 40 and the WI 38 SV 40 cell lines. The immunologically detectable switch-over has been confirmed by measuring the apparent Michaelis constant and the heat stability of the AP from normal and transformed cells. Liver-like AP is heat labile and has an apparent Michaelis constant for p-nitrophenylphosphate (about 4.0 X 10(-4) M). The placenta-like AP shows heat stability and a lower apparent KM (about 2.2 X 10(-4) M). The appearance of the so-called Regan enzyme of AP in some human tumors in vivo is discussed in this connection.