A High-Performance Liquid Chromatographic Method for The Simultaneous Determination of Nicardipine and Its Pyridine Metabolite II in Plasma

1 The antihypertensive efficacy of a long acting formulation of the calcium channel blocking drug, nicardipine, was assessed using clinic and ambulatory (Remler M2,000) blood pressure measurements.2 Eleven patients with essential hypertension (mean ± s.e. mean; 173 ± 6.6/103 ± 1.9 mmHg) completed a randomised double-blind, placebo-controlled, cross-over study. The dose of nicardipine used was 60 mg twice daily for 4 weeks. 3 Mean ambulatory blood pressure was reduced from 164 ± 5.3/97 ± 2.9 to 151 ± 5.2/88 + 2.4 mmHg (P < 0.01); this effect was shown to be sustained for 8 h after the morning dose. Mean ambulatory heart rate was not significantly affected by treatment. 4 Clinic lying systolic blood pressure was reduced on treatment from 169 ± 7.1 to 157 ± 5.9 mmHg (P < 0.2) and diastolic blood pressure from 99 ± 3.6 to 89 ± 3.9 mmHg (P < 0.05). S One patient was withdrawn because of dizziness and flushing while on nicardipine; vasodilatory side effects such as headache, palpitations and flushing on nicardipine were noted by three patients. 6 We conclude that the long acting formulation of nicardipine studied in a dose of 60 mg twice daily is effective as monotherapy and is relatively well tolerated in mild hypertension. 7 This study highlights the importance of ambulatory blood pressure measurement in detecting significant changes in blood pressure, thereby permitting the study of small numbers of patients.Keywords ambulatory blood pressure measurement hypertension nicardipine calcium channel blockers

Section: Methodsmentioning

confidence: 99%

The effect of slow‐release nicardipine on ambulatory and clinic blood pressure in mild hypertension.

Cox

Ryan

O’Brien

et al. 1989

“…Nicardipine was assayed using an h.p.l.c. method which allowed separation of the parent drug and its haemodynamically inactive metabolite (Wu et al, 1984).…”

Section: Methodsmentioning

confidence: 99%

Noninvasive assessment of the haemodynamic effects of nicardipine in normotensive subjects.

Campbell¹,

Kelman²,

Hillis³

1985

1 Calcium antagonists reduce myocardial contractility in vitro. Nicardipine is a dihydropyridine derivative with enhanced selectivity for vascular smooth muscle. 2 We have studied the pharmacokinetics and the haemodynamic effects that occur in man following bolus intravenous administration of nicardipine. 3 Ten normotensive male subjects received either nicardipine or placebo i.v., allocated in a randomised double-blind manner, over 60 s 4 Plasma nicardipine concentration, blood pressure, heart rate, and systolic time intervals were measured before dosing and at frequent intervals between I and 360 min post dosing. 5 At 160 jug kg-', adequate plasma levels of nicardipine were obtained to permit analysis of individual pharmacokinetic variables, and significant and consistent haemodynamic effects were seen. 6 After injection ofnicardipine, systolic BP and the QS2 (measure of total electromechanical systole) and QT intervals were not altered. 7 The changes in BP and heart rate were consistent with arteriolar vasodilatation. 8 The changes in PEP and LVET suggest an increase in cardiac contractility, which is unlikely to be a direct effect of nicardipine on the myocardium but rather a result of afterload reduction. 9 The close correlation of nicardipine plasma level with haemodynamic effect should permit accurate dose titration. 10 The net increase in contractility should allow nicardipine to be administered safely with fi-adrenoceptor blocking drugs.Keywords blood pressure calcium antagonist heart rate nicardipine systolic time intervals concentration effect modelling

“…(Higuchi et al, 1975) and high-performance liquid chromatography (h.p.l.c.) (Wu et al, 1984). Using g.c., nicardipine was quantified following oxidation to a pyridine analogue metabolite (M5).…”

Section: Subjectsmentioning

confidence: 99%

The metabolism and pharmacokinetics of nicardipine hydrochloride in man.

Graham¹,

Dow²,

Hall³

et al. 1985

1 Studies have been carried out to investigate the disposition of nicardipine hydrochloride following intravenous and oral administration to male volunteers. 2 Following oral administration of a radiolabelled dose, nicardipine was shown to be rapidly and extensively metabolised and to be rapidly eliminated from plasma. 3 After intravenous infusion of nicardipine at 5 mg-' for 3 h, plasma levels declined biexponentially, and clearance values were of the same order as hepatic blood flow. 4 With repeated oral administration, 20 mg three times daily for 28 days, plasma levels rose over the first 3 days of administration and then declined to some extent. Possible reasons for this decline are discussed. 5 Steady-state plasma levels and bioavailability show a nonlinear relationship with doses over the range 10-40 mg three times daily. 6 Food consumption has been shown to reduce the bioavailability of nicardipine when the food is taken before or at the same time as nicardipine administration.