Efficacy and safety of Minipress XL, a new once-a-day formulation of prazosin

Singleton, W. S.; Dix, Robert K.; Monsen, Lisa; Moisey, D.M.; Levenstein, Marcia; Bottiglieri, Denise F.; Silver, Lester

doi:10.1016/0002-9343(89)90113-7

Cited by 7 publications

(4 citation statements)

References 1 publication

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“…Together, our findings provide a better understanding of the ciliary body physiology, completing a preclinical translational research addressed to combat glaucoma. Remarkably, a therapeutic strategy resulting from combining melatonin, sold as a supplement and lacking collateral effects even at high doses in the eye (Rosenstein et al, 2010;Sanchez-Barcelo, Mediavilla, Tan, & Reiter, 2010), and prazosin, approved for the therapy of blood hypertension (Brogden et al, 1977;Mallorga, Buisson, & Sugrue, 1988;Singleton et al, 1989;Torvik & Madsbu, 1986), could readily enter into clinical trials to assay for safety and efficacy in humans.…”

Section: Discussionmentioning

confidence: 99%

Adrenergic-melatonin heteroreceptor complexes are key in controlling ion homeostasis and intraocular eye pressure and their disruption contributes to hypertensive glaucoma

Alkozi

Navarro

Aguinaga

et al. 2019

Preprint

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AbstractMelatonin regulates intraocular pressure (IOP) whose increase leads to glaucoma and eye nerve degeneration. Aiming at elucidating the role of melatonin receptors in humour production and IOP maintenance, we here demonstrate that glaucoma correlates with disassembly of α1-adrenergic/melatonin receptor functional units in cells producing the aqueous humour. Remarkably, α1-adrenoceptor-containing complexes do not coupled to the cognate Gq protein and, hence, phenylephrine activation of these receptors does not lead to Ca2+ mobilization. Functional complexes are significantly decreased in models of glaucoma and, more importantly, in human samples of glaucoma patients (GP). In such glaucomatous conditions phenylephrine produces, via α1-adrenoceptor activation, an increase in cytoplasmic [Ca2+] that is detrimental in glaucoma. The results led to hypothesize that using melatonin, a hypotensive agent, plus blockade of α1-adrenergic receptors may normalize pressure in glaucoma. Remarkably, co-instillation of melatonin and prazosin, a α1-adrenergic receptor antagonist, results in long-term decreases in IOP in a well-established animal model of glaucoma. The findings are instrumental to understand the physiological function of melatonin in the eye and its potential to address eye pathologies by targeting melatonin receptors and their complexes.

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Section: Discussionmentioning

confidence: 99%

Adrenergic-melatonin heteroreceptor complexes are key in controlling ion homeostasis and intraocular eye pressure and their disruption contributes to hypertensive glaucoma

Alkozi

Navarro

Aguinaga

et al. 2019

Preprint

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“…Volume depletion by diuretics or bradycardia caused by p-blockers may be contributing factors. A modifiedrelease dosage form of prazosin appears to reduce the likelihood of this complication) 19] Exercise function appears unimpaired. Other cardiovascular symptoms include palpitation and myocardial ischaemia.l 4 -61 Although dosages of 40 to 80 mg/kg/day of doxazosin for 6 to 18 months have been associated with an increased incidence of myocardial necrosis in rats and mice, there is no evidence of similar lesions occurring in humans.…”

Section: Cardiovascular Toxicitymentioning

confidence: 99%

Adverse Effects of ??1-Adrenergic Blocking Drugs

1994

Drug Safety

103

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Earlier nonselective alpha 1-adrenergic blocking drugs such as phentolamine and phenoxybenzamine are now restricted to the pharmacological management of alpha 1-adrenergic crisis and phaeochromocytoma. Prazosin, the first selective alpha 1-blocker approved for the treatment of hypertension, became available in the mid-1970s. Additional alpha 1-blockers such as doxazosin and terazosin have been introduced during recent years. The undesirable effects of all members of this class are similar. Most adverse events can be attributed to reversible competitive antagonism of postsynaptic alpha 1-adrenergic receptors in tissues that sustain high levels of alpha-adrenergic sympathetic tone, e.g. resistance arteries, capacitance veins and the urinary bladder outflow tract. Orthostatic hypotension with a sensation of intense faintness and occasional syncope, can occur shortly after the initial dose. Aggravating factors include upright posture, intravascular volume depletion and concurrent administration of other medications that lower blood pressure, including all other classes of antihypertensive drugs. The problem is reduced or avoided by the choice of low starting doses, beginning treatment at bedtime and by minimising other risks. Among overall adverse effects, asthenia, dizziness, faintness and syncope predominate and occur in 10 to 20% of patients, leading to discontinuation of therapy in about half that number. Infrequent adverse events include headache, drowsiness, palpitations, urinary incontinence and priapism. Some patients experience a 1 to 2kg bodyweight gain which may be associated with secondary hyperaldosteronism. Tolerance appears to develop to the benefits of alpha 1-blockade in patients with congestive heart failure, but not in hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Our data suggest the potential suitability of P-GS as a treatment of hypertension during the third trimester of pregnancy. The controlled-release seems to provide more consistent drug effects and improve patient compliance (22). In our opinion, this treatment could represent an alternative to methyldopa as a first treatment of pregnancy-associated hypertension.…”

Section: Resultsmentioning

confidence: 85%

Disposition of a new rate-controlled formulation of prazosin in the treatment of hypertension during pregnancy: transplacental passage of prazosin

Bourget¹,

Fernandez

Edouard

et al. 1995

European Journal of Drug Metabolism and Pharmacokinetics

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Prazosin (PRZ) in conventional tablet form (P-CT) has the disadvantages of a relatively short terminal half-life, a slight solubility in water and the well-recognized adverse effect of symptomatic orthostatic hypotension. The pharmacokinetic study of a new rate-controlled formulation of prazosin (Prazosin-Gastrointestinal System: P-GS) was performed in 9 pregnant women during the third trimester of pregnancy. Patients had persistent elevation of blood pressure. The subjects gave their informed consent for oral administration of 1 daily dose of 5 mg P-GS at 8 a.m. A first analysis period on day 1 enabled definition of the initial pharmacokinetic behavior of the drug, while the aim of a second was to evaluate its fate at plateau. The clinical course of both mother and fetus was subsequently monitored. This was an open, non-randomized study, each patient serving as her own control. For 3 patients, we aimed to determine the possible transplacental passage of PRZ at delivery. PRZ levels were measured by HPLC and data were analysed by noncompartmental linear pharmacokinetic methods. The data show: (i) P-GS was well tolerated by all patients and there were no significant changes in fetal heart rate during the study. (ii) A significant decrease in diastolic blood pressure was observed after the 36th hour following the first dose of P-GS while a reduction in systolic blood pressure was observed on day 4. (iii) An approximated relative bioavailability (f'P-GS) of 36.5% was calculated. P-GS appears to have a lower bioavailability than P-CT in women of similar gestational age. (iv) Both Cmax and AUC0-->infinity are significantly increased at plateau. Further, terminal half-life is increased with regard to the value determined with P-CT. No accumulation of PRZ was noted at steady-state. (v) P-GS is an example of an oral zero-order absorption product that offers one approach to control and improve the outcome of hypertensive therapy during pregnancy. This treatment could represent an alternative to methyldopa as a first treatment of pregnancy-associated hypertension. (vi) There is a slight transplacental passage of the drug (of the order of 10-20%).

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Efficacy and safety of Minipress XL, a new once-a-day formulation of prazosin

Cited by 7 publications

References 1 publication

Adrenergic-melatonin heteroreceptor complexes are key in controlling ion homeostasis and intraocular eye pressure and their disruption contributes to hypertensive glaucoma

Adrenergic-melatonin heteroreceptor complexes are key in controlling ion homeostasis and intraocular eye pressure and their disruption contributes to hypertensive glaucoma

Adverse Effects of ??1-Adrenergic Blocking Drugs

Disposition of a new rate-controlled formulation of prazosin in the treatment of hypertension during pregnancy: transplacental passage of prazosin

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