Steady state investigation of possible pharmacokinetic interactions of moxonidine and glibenclamide

Müller, M; Weimann, H; Eden, Gabriele; Weber, W.; Michaelis, K.; Dilger, C; Achtert, G.

doi:10.1007/bf03188809

Cited by 6 publications

(4 citation statements)

References 6 publications

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“…Three studies were conducted to determine possible pharmacokinetic interactions between moxonidine and hydrochlorothiazide (1 30), digoxin (94), and glibenclamide (90). Co-administration of moxonidine did not significantly change the pharmacokinetics of digoxin and hydrochlorothiazide; nor did digoxin and hydrochlorothiazide alter the pharmacokinetics of moxonidine.…”

Section: Drug Interactionsmentioning

confidence: 99%

Moxonidine: A Second‐generation Central Antihypertensive Agent

Ernsberger

Elliott

Weimann³

et al. 1993

Cardiovascular Drug Reviews

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Rational treatment of primary hypertension remains elusive, owing to a lack of knowledge about the pathogenesis of blood pressure elevation. Established hypertension is associated with well-described cardiovascular hemodynamic changes. Because the cardiovascular system is self-regulating, the action of an antihypertensive on one of the regulatory mechanisms induces changes in others. A drug-induced decrease of the elevated peripheral resistance leads to compensatory reflex mechanisms. The use of centrally acting drugs avoids compensatory neural reflexes. Furthermore, the participation of the central and autonomic nervous systems in the pathogenesis of hypertension is probable. The development of drugs aimed at controlling the central nervous system (CNS) would, therefore, be reasonable. The use of a,-adrenoceptor agonists, such as clonidine, as antihypertensive agents has declined. The mean reason being a high rate of side effects such as sedation, dry mouth with marked reduction in salivary flow, and other nonspecific effects. The mode of action was explained by stimulation of both pre-and postsynaptic a,-adrenoceptors within the CNS . However, recent investigations have clearly demonstrated that centrally acting drugs like clonidine and moxonidine induce their antihypertensive effects primarily by high affinity binding at the imidazoline receptors. Most of the side effects are induced by an action at aw,-receptors. The difference between clonidine and moxonidine is moxonidine's pronounced selectivity for imidazoline rather than ctzreceptors. Moxonidine and other related compounds may reestablish the use of centrally active drugs in antihypertensive therapy.~ ~~~

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Section: Drug Interactionsmentioning

confidence: 99%

Moxonidine: A Second‐generation Central Antihypertensive Agent

Ernsberger

Elliott

Weimann³

et al. 1993

Cardiovascular Drug Reviews

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“…In addition, several studies demonstrate the absence of any interaction between glibenclamide and pirprofen, acarbose, lisinopril, ibuprofen, ranitidine, trimethoprim-sulfamethoxazole, vinpocetine, enoxacin, carvedilol and moxonidine GERARD et al 1984;DANHOF et al 1986;KUBACKA et al 1987;SJOEBERG et al 1987;GRANDT et al 1989;GÖBEL et al 1990;MÜLLER et al 1993;HARDER et al 1993). With ranitidine, however, glucose and insulin concentrations are elevated.…”

Section: F) Pharmacokinetic Interactionsmentioning

confidence: 93%

Clinical Pharmacology of Sulfonylureas

Groop¹,

Neugebauer²

1996

Oral Antidiabetics

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“…The specific transport systems responsible for moxonidine active tubular secretion remain undetermined. It was reported that pharmacokinetics of moxonidine was not altered with coadministration of glibenclamide, which is a known P-glycoprotein inhibitor and substrate (Muller et al, 1993). A recent study also found that quinidine sulfate, a potent inhibitor of organic cation secretion as well as a inhibitor of P-glycoprotein, does not affect the renal clearance of moxonidine (Wise et al, 2002).…”

Section: Moxonidine Metabolism In Humansmentioning

confidence: 98%

Metabolism and Disposition of the Antihypertensive Agent Moxonidine in Humans

Abraham²,

Lindsay³

et al. 2003

Drug Metab Dispos

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ABSTRACT:The metabolism and pharmacokinetics of moxonidine, a potent central-acting antihypertensive agent, were studied in four healthy subjects after a single oral administration of approximately 1 mg (ϳ60 Ci) of [ 14 C 3 ]moxonidine. Moxonidine was rapidly absorbed, with peak plasma concentration achieved between 0.5 to 2 h postdose. The maximal plasma concentration and the area under the curve of unchanged moxonidine are lower than those determined for radioactivity, indicating presence of circulating metabolite(s). The total recovery of radiocarbon over 120 h ranged from 99.6 to 105.2%, with 92.3 to 103.3% of the radioactivity excreted in the urine and only 1.9 to 7.3% of the dose excreted in the feces. Thus, renal elimination represented the principal route of excretion of radioactivity. Metabolites of moxonidine were identified in urine and plasma samples by high performance liquid chromatography and liquid chromatography-tandem mass spectrometry. Oxidation of moxonidine on the methyl group or on the imidazoline ring resulted in the formation of hydroxymethyl moxonidine, hydroxy moxonidine, dihydroxy moxonidine, and dehydrogenated moxonidine. Metabolite profiling results indicated that parent moxonidine was the most abundant component in the urine. The dehydrogenated moxonidine was the major urinary metabolite as well as the major circulating metabolite. Moxonidine also underwent phase II metabolism, generating a cysteine conjugate. In summary, moxonidine is well absorbed after oral administration. The major clearance pathway for moxonidine in humans is via renal elimination. Furthermore, seven metabolites were identified with three metabolites unique to humans.Moxonidine is a new antihypertensive agent that acts on central nervous system imidazoline receptors to decrease sympathetic nervous system tone (Ernsberger et al., 1992;Prichard and Graham, 1996). It has been marketed throughout Europe for the treatment of hypertension. The safety and efficacy of moxonidine in hypertension patients has been established (Ollivier et al., 1992;Sides et al., 1998). In comparison to clonidine and rilmenidine, moxonidine has fewer adverse effects such as dry mouth and sedation because it is considerably more selective for the I 1 receptor than the ␣ 2 receptor that is associated with these indicated side effects (Yu and Frishman, 1996). In elderly patients, the clearance of moxonidine is reduced, and the area under the curve of unchanged drug is greater in comparison with younger patients suggesting the existence of an age-related decrease in metabolism (Theodor et al., 1996). Moxonidine has a relatively short half-life (about 2-3 h). However, it has long duration of effect and is given only once daily clinically. There is no clear correlation between the pharmacokinetics and pharmacodynamic effect of moxonidine.To determine whether the long duration of moxonidine is attributed to the production of active metabolite(s), efforts were undertaken to identify and synthesize major metabolites of moxonidine and test their ph...

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Steady state investigation of possible pharmacokinetic interactions of moxonidine and glibenclamide

Cited by 6 publications

References 6 publications

Moxonidine: A Second‐generation Central Antihypertensive Agent

Moxonidine: A Second‐generation Central Antihypertensive Agent

Clinical Pharmacology of Sulfonylureas

Metabolism and Disposition of the Antihypertensive Agent Moxonidine in Humans

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