Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new verelan research articles will be listed here shortly after becoming available to us.
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Medical research on verelan
Chrono: a community-based hypertension trial of a chronotherapeutic formulation of verapamil.
Am J Ther. 2002 Nov-Dec; 9(6): 476-83
Prisant LM, Black HR, Messerli F, Weber M
An open-label, multicenter, dose-titration study evaluated 2,556 patients with stage I or II essential hypertension (untreated or previously treated with one antihypertensive agent) to assess the effect of a chronotherapeutic formulation of verapamil (Verelan PM) designed to provide maximum plasma concentrations in the midmorning hours. After starting with 200 mg/d at bedtime, the dose of Verelan PM was titrated to a maximum of 400 mg/d at 4-week intervals to achieve a target blood pressure (BP)
Pharmacology of cardiovascular chronotherapeutic agents.
Am J Hypertens. 2001 Sep; 14(9 Pt 2): 296S-301S
Smith DH
Although sudden cardiac death, myocardial infarction, or stroke can occur at any time of day, event rates increase during the waking hours, particularly in the morning. In most people-both normotensive and hypertensive-blood pressure (BP) rises rapidly in the early morning hours, the time when most individuals wake and begin their day. This rise in BP corresponds to increased secretion of catecholamines and increased plasma renin activity. Thus, vascular tone and total peripheral resistance increase in the morning hours, and BP rises as a result. At the same time, heart rate increases. In the late morning or early afternoon, BP reaches its peak. After that, BP declines, falling 15 to 20 mm Hg between about 8 PM and 2 AM, the time when BP is usually lowest. These findings have led to an interest in chronotherapy for hypertension. A major objective of chronotherapy for hypertension is to deliver the drug in higher concentrations during the early-morning post-awakening period, when BP is highest, and in lesser concentrations during the middle of a sleep cycle, when BP is low. Traditional sustained-release pharmacologic agents, which deliver a near-constant drug concentration, were not designed to complement the circadian pattern. There are currently two antihypertensive agents, Verelan PM (verapamil HCl) and Covera HS (verapamil HCl), that provide chronotherapy for hypertension. These drugs use novel delivery systems that provide 24-h BP control while maximizing drug concentrations in the morning and minimizing drug concentrations during sleep.
Clin Cardiol. 1996 Mar; 19(3): 205-11
Gebara OC, Jimenez AH, McKenna C, Mittleman MA, Xu P, Lipinska I, Muller JE, Tofler GH
Stress-induced hemodynamic and hemostatic responses may acutely trigger atherosclerotic plaque disruption and thrombosis leading to myocardial infarction. This study was designed to evaluate the responses to three stressors and to determine if once-daily sustained release verapamil (Verelan) modified these responses. We studied 13 patients with mild to moderate hypertension in a randomized, double-blind, placebo-controlled crossover trial. After 4 weeks of therapy, patients were evaluated following assumption of the upright posture, mental stress, and cold pressor test. During placebo, the stressors produced an increase in systolic pressure (144 +/- 2 to 167 +/- 3 mmHg, p < 0.001), heart rate (70 +/- 2 to 77 +/- 2 beats/ min, p < 0.001), and platelet aggregability to adenosine diphosphate (threshold concentration fell from 2.8 +/- 0.4 to 1.9 +/- 0.1 microM, p = 0.05) and epinephrine (3.4 +/- 0.9 to 1.6 +/- 0.6 microM, p < 0.001). Verapamil lowered systolic pressure at baseline (144 +/- 2 to 134 +/- 2 mmHg, p < 0.001), and after stress (167 +/- 3 to 154 +/- 3 mmHg, p < 0.001), but did not alter the absolute increase with stress. During verapamil, platelet reactivity did not increase with stress, and the post-stress response to epinephrine was reduced (higher threshold concentration) compared with placebo (3.9 +/- 1.3 vs. 1.5 +/- 0.3 microM, p = 0.05). Verapamil also reduced the response to collagen (increased lag time) at baseline and after stress (111 +/- 9 vs. 91 +/- 3 s, p < 0.01). We conclude that verapamil blunted potentially harmful stress-induced hemodynamic and hemostatic changes. Further studies are required to determine whether these effects translate into a lower incidence of acute cardiovascular events.
Large-Scale Postmarketing Surveillance of Hypertensive Patients Treated with Verapamil.
Am J Ther. 1995 Jul; 2(7): 455-461
Cobb MM, Johnson D, Gallo J, Crawley JA, Cargo PH, Lefkowitz MP
BACKGROUND: In general clinical practice, physicians prescribe calcium channel blockers to a wide range of patients with differing demographic characteristics and hypertension history. This study was undertaken to investigate the effectiveness and safety of sustained-release verapamil (Verelan((R)), verapamil HCl) in patients with essential hypertension, studied under "usual use" conditions. METHODS: In this prospective, open-label, postmarketing surveillance study, 25 089 patients with hypertension received once-daily verapamil therapy for 4 weeks, during which they were evaluated by 8106 physicians at baseline and at two follow-up visits (weeks 2 and 4). In this study, hypertension was defined as an average sitting diastolic blood pressure (DBP) of greater-than-or-equal 90 mm Hg at baseline. Previously diagnosed hypertensive patients with a sitting DBP
Sustained-release verapamil formulations for treating hypertension.
J Clin Pharmacol. 1992 May; 32(5): 455-62
Frishman WH, Lazar EJ
Verapamil, the first calcium-channel blocker to be introduced for clinical use, is a major drug used for the treatment of systemic hypertension. During the past 10 years, the use of verapamil for hypertension has produced a considerable clinical database to support the efficacy and safety of the agent in many patients. Because of its short half-life, verapamil was originally administered 3 to 4 times daily. During the past decade, a sustained-release formulation of verapamil has been marketed in the US. This product allows for once-daily dosing up to 240 mg/d; however, when higher doses are needed, this sustained-release formulation should be administered twice daily. In addition, the medicine should be taken with food to avoid the high peak blood levels of verapamil, which appears to be related to the delivery system. A new pellet-filled capsule formulation of verapamil (Verelan, Lederle, Wayne, NJ and Wyeth-Ayerst, Philadelphia, PA) is available and provides controlled absorption, 24-hour blood pressure control, improved peak-to-trough plasma levels, and once-daily dosing regardless of dosage size. Prolonged-release verapamil can be taken without food.
Calcium antagonists in cardiology: update on sustained-release drug delivery systems.
Clin Cardiol. 1991 Dec; 14(12): 947-50
Michelson EL
One limitation of standard oral formulations of calcium antagonists has been the need for multiple daily dosing. Sustained-release dosage forms permit simpler regimens and a smoother therapeutic effect. Differences in drug pharmacokinetic and pharmacodynamic properties have led to development of several sustained-release delivery systems. Three major types are available: the osmotic pump, coated pellet, and slow-dissolving material released from a matrix. Each is currently utilized with specific calcium antagonists. The osmotic pump system with nifedipine (Procardia XL, Pfizer) allows once-daily dosing as well as improvements in certain side effects. Verapamil is available in formulations employing dissimilar release systems. The original sustained-action products (Calan SR, Searle; Isoptin SR, Knoll) utilize a matrix system; a subsequent product (Verelan; Lederle, Wyeth-Ayerst, A. H. Robins) utilizes timed-release pellets. Importantly, clinical efficacy appears to be maintained with these several drugs and formulations for their approved indications. Although a specific formulation may alter the absorption, metabolism, excretion, and blood levels of a drug, it does not alter basic drug properties. Thus, the major impact of sustained-release drug delivery system lies in potential compliance improvement and possible reduction of side effects related to serum drug profiles.
Newer antihypertensive agents.
Postgrad Med. 1991 Apr; 89(5): 75-81, 84, 89
Rey AM, Grauer K, Gums JG
Three recent additions to the list of antihypertensive agents have been approved for use as monotherapy or in combination with other drugs. Betaxolol hydrochloride (Kerlone) maintains its effect for 24 hours, making it a true once-a-day beta blocker. Penbutolol sulfate (Levatol) is as effective as other beta blockers and diuretics. Doxazosin mesylate (Cardura), a selective alpha 1 blocker, also allows once-a-day dosing and has produced favorable changes in lipid profiles. Two new drug delivery systems, one for verapamil hydrochloride (Verelan) and one for extended-release nifedipine (Procardia XL), allow less frequent dosing and may offer other advantages, such as greater compliance and a more tolerable side-effect profile.
Dose proportionality of pharmacokinetics with a cr-verapamil formulation.
Eur J Drug Metab Pharmacokinet. 1991; Spec No 3: 304-11
Mulligan S, Devane J, Martin M
The relatively short half life of verapamil necessitates divided daily dosing in the treatment of angina, hypertension and arrhythmia. To reduce dosing frequency and increase patient compliance and therapeutic efficacy, a controlled-release once-daily verapamil formulation (Verelan) has been developed in three dosage strengths, 120 mg, 240 mg and 360 mg. In order to investigate the dose linearity of this formulation in the 120 mg and 360 mg dose range, un unblinded, crossover, comparative evaluation of the three dosage strengths was performed in a population of 27 male volunteers. Each treatment period lasted nine days with a minimum of 7 days between periods. On Days 1 and 2 of each treatment period, the single dose phase was evaluated following administration of medication on Day 1 only with regular blood sampling over the 48 hour period. On Days 3 and 7 inclusive, the five-day steady phase was evaluated. Mean plasma profiles following administration of each dose demonstrated extended verapamil absorption up to 24 hours after dosing. In both the single dose and steady state phases a linear relationship was observed between increasing dose and pharmacokinetic response over the dose range of 120 mg and 360 mg. This linearity in response with increasing dose is in contrast to the non-linearity of verapamil's pharmacokinetics with conventional verapamil formulations previously described by an number of workers and may be due to a saturation of verapamil's hepatic first pass metabolic pathway.(ABSTRACT TRUNCATED AT 250 WORDS)