[Pharmacokinetics and pharmacodynamics of slow release tablet of diltiazem in hypertensive patients with various renal functions].

Twenty hypertensive patients were equally divided into 2 groups: A) with normal renal function (NRF) and B) with impaired renal function (IRF) according to creatinine clearance, blood urea nitrogen and creatinine levels. The pharmacokinetic and pharmacodynamic effects of diltiazem (Dil, 90 mg, bid x 7 d, p.o.) were studied. The pharmacokinetic parameters in IRF patients (Ka 0.7 +/- 0.2 h-1, T 1/2e 3.7 +/- 0.7 h, Cmax1 45 +/- 4 ng.ml-1, Tmax1 3.1 +/- 0.4 h) did not differ from those in NRF patients (0.7 +/- 0.5 h-1, 4.1 +/- 1.3 h, 41 +/- 5 ng.ml-1 and 3.4 +/- 0.4 h, P > 0.05). Antihypertensive efficacy of Dil in patients with IRF was similar to that in those with NRF, and the hypotensive effect lasted over 24 h. The plasma Dil concentrations were strongly correlated with a decrease in BP in both groups. It was concluded that IRF did not affect the disposition of slow release Dil tablet under a steady state. No dosage adjustment of Dil is necessary in hypertensive patients with IRF.

[Pharmacokinetics and pharmacodynamics of diltiazem floating tablets].

Floating tablet is a new type of delayed-action preparations. The present study was aimed at pharmacokinetic and hemodynamic effects of diltiazem floating tablet in 8 healthy volunteers. Each subject received po 90 mg diltiazem floating and normal tablets in a crossover design. For floating tablets the T1/2 (6.4 +/- 4.4 h) and Cmax (56 +/- 23 ng.ml-1) were longer and lower than those of normal tablets (2.3 +/- 1.1 h and 96 +/- 30 ng.ml-1, P < 0.01), respectively. AUC of the 2 forms were similar, suggesting that they had same bioavailability. Diltiazem lowered the blood pressure of the subjects. Although there was no significant difference between the 2 formulations in maximal decreases of systolic and diastolic blood pressures, the duration of hypotension was longer with floating tablets than that with normal ones. There was a positive correlation between diltiazem concentration and its hypotensive action. Thus, administration of floating tablets twice a day may be effective in controlling the blood pressure of hypertensive patients.

[Hypotensive action of l-stepholidine in relation of dopamine receptors].

Spontaneously hypertensive (SH) and 2 kidney 1 clip hypertensive (2k1cH) rats were treated with ig l-stepholidine (SPD) 200 mg/(kg.d). Two wk after medication, the average blood pressure (BP) of SH and 2k1cH were 21.3 +/- 3.8 and 25.5 +/- 3.8 kPa lower than their controls respectively. The concentration of serum prolactin in treated SH and 2klcH decreased by 48% and 54%, respectively with its decrease of BP. The levels of plasma norepinephrine and epinephrine were increased and the excretion of urinary sodium was reduced or not changed. Since the level of prolactin is a biochemical index of central dopamine receptor (D-2) activity, so these results suggest that the regulation of central dopamine receptors may take part in hypotensive action of ig SPD and the peripheral dopamine receptors are neither agonistic to SPD nor involved in hypotensive action.

Blood pressure response of two types of Goldblatt hypertensive rats to enalapril.

Enalapril (MK-421), a new angiotensin converting enzyme inhibitor, reduces the blood pressure in one-kidney, one-clip hypertensive rats at 30 mg/kg p.o. (n = 12). On the fifth day and during the fifth week after renal artery constriction, systolic blood pressure decreased from 196 +/- 4 and 240 +/- 5 mm Hg pretreatment to 159 +/- 8 and 225 +/- 3 mm Hg, respectively (p less than 0.001 and 0.05, respectively) and was maintained at this level for about 8 h. Serum angiotensin converting enzyme activity was significantly inhibited by enalapril. Similarly, enalapril (30 mg/kg p.o.) in two-kidney, one-clip hypertensive rats (n = 18) on the fifth day and during the fifth week after operation resulted in a decrease in blood pressure from 162 +/- 5 and 217 +/- 5 mm Hg to 117 +/- 6 and 120 +/- 7 mm Hg, respectively, to the preoperative normotensive level (113 +/- 1 mm Hg). These results indicate that the renin-angiotensin system may play an important role in the pathogenesis of two-kidney, one-clip hypertensive rats. However, in the pathogenesis of one-kidney, one-clip hypertensive rats, other mechanisms seem to be involved besides the renin-angiotensin system.