Pharmacokinetic and pharmacodynamic parameters in patients treated with nitrendipine.

Abstract

Nitrendipine (BAY e 5009) is a new calcium channel blocker with a marked effect on excitation-contraction coupling in different types of muscle cells. It has many similarities to the established agent, nifedipine. In the present study, nitrendipine was evaluated in a double-blind within-patient comparison. Twelve patients with essential hypertension were given nitrendipine 20 mg or 40 mg orally for three weeks following a 1-week placebo period. After a second 1-week placebo period, there was a crossover to the alternative dosage (20 or 40 mg respectively), and active therapy was again given for 3 weeks. Both doses of nitrendipine caused a significant and equal reduction of arterial pressure, which persisted for at least 24 hours. Only the highest dose caused an increase in heart rate. There were a few reports of headaches, flushing, and palpitation, particularly after the 40 mg dose. There was a significant correlation between the reduction of mean arterial pressure and the log plasma concentration (20 mg: r = -0.88, p less than 0.01; 40 mg: r = -0.94, p less than 0.001). There was a linear relationship between the area under the curve and the oral dose, indicating that liver enzyme saturation had not occurred. There was no accumulation of nitrendipine in plasma during 3 weeks of treatment.

A double‐blind randomized cross‐over study of the efficacy and tolerability of nifedipine and nitrendipine in the treatment of mild to moderate hypertension.

“…In accord with a previous study, heart rate was not affected by chronic administration of nitrendipine (Hansson et al, 1983), whereas pulse rates fell on nifedipine, achieving statistical significance in the supine position. Adverse events necessitating withdrawal were observed equally on each drug and neither influenced body weight, blood biochemistry or haematology.…”

“…Nitrendipine has been produced in an attempt to provide 24 h blood pressure control from once daily administration and to reduce unwanted side-effects. An early study suggested that 20 mg orally once daily was effective for 24 h and that increasing the dose to 40 mg once daily conferred no further benefit (Hansson et al, 1983). However, this was not the case in our study and the withdrawal rate due to vasodilator side-effects was similar to that seen with nifedipine; however, in the present study the non-responders received nitrendipine 20 mg orally twice daily.…”

“…The results of this experiment demonstrate that nitrendipine is as effective as nifedipine in lowering blood pressure, although despite claims that nitrendipine is effective once daily (Hansson et al, 1983), this study suggests that in a dose of 20 mg given orally daily blood pressure control was not satisfactory. In accord with a previous study, heart rate was not affected by chronic administration of nitrendipine (Hansson et al, 1983), whereas pulse rates fell on nifedipine, achieving statistical significance in the supine position.…”

Pharmacokinetics, bioavailability, metabolism and acute and chronic antihypertensive effects of nitrendipine in patients with chronic renal failure and moderate to severe hypertension.

“…Nitrendipine (the racemate of 3-ethyl 5-methyl 1,4-demonstrated to last for up to 22 h in patients with mild dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine to moderate hypertension (Dal Canton et al, 1986; dicarboxylate) is a dihydropyridine calcium channel Hansson et al, 1983;Wandel et al, 1987). Thus, it has blocker which has been introduced recently as an antibeen claimed that once or twice daily oral administration hypertensive drug.…”

Application of stable isotope methodology to study the pharmacokinetics, bioavailability and metabolism of nitrendipine after i.v. and p.o. administration.

“…dimethyl-4-(3-nitrophenyl)3,5-pyridine-dicar-Published data on its pharmacokinetics are limited boxylate) is a calcium antagonist with potent and somewhat equivocal. Thus after intravenous vasodilating properties (Kazda et al, 1984; administration terminal half-lives in the order of Correspondence: Professor Dr M. Eichelbaum, Dr Margarete Fischer-Bosch-Institut fur klinische Pharmakologie, Auerbachstrasse 112, D-7000 Stuttgart 50, Germany 3 to 4 h have been reported (Raemsch & Sommer, 1984), whereas following oral administration terminal half-lives ranged from 4 h to 11 h (Kann etal., 1984;Raemsch & Sommer, 1984;Hansson et al, 1983Hansson et al, , 1984. Furthermore, after intravenous infusion for 20 h half-lives of the order of 12 h have been observed (Raemsch et al, 1987).…”