Pharmacokinetics of molsidomine in humans

Ostrowski, Janusz; Resag, K.

doi:10.1016/0002-8703(85)90670-2

Cited by 15 publications

(4 citation statements)

References 2 publications

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“…The pharmacokinetic parameters of molsidomine in the solution were in accordance with data in the literature [10,11,12,13,14,15]. So far, no significant violation of dose linearity has been described.…”

Section: Discussionsupporting

confidence: 86%

Pharmacokinetic profile of a novel slow release preparation of molsidomine

Rietbrock

Keller‐Stanislawski

Thürmann

et al. 1992

Eur J Clin Pharmacol

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A novel slow release preparation containing 24 mg molsidomine has been investigated in 6 healthy subjects. Individual concentration/time-profiles after the tablet showed two separate concentration peaks at 2.2 h and 15.0 h. The relative bioavailability of the slow release preparation in comparison to an aqueous solution of molsidomine was 0.67. The in vivo dissolution profile revealed either a progressive decrease in dissolution velocity caused by altered physico-chemical conditions in the ileum and the colon or a progressive reduction in the absorption constant. In all subjects deconvolution revealed a punctual increase in absorption about 15 h post-dose, coinciding with the second peak of the concentration/time-profile. Therapeutic plasma levels of molsidomine (greater than 5 ng.ml-1) were not maintained over 24 h by this slow release formulation.

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Section: Discussionsupporting

confidence: 86%

Pharmacokinetic profile of a novel slow release preparation of molsidomine

Rietbrock

Keller‐Stanislawski

Thürmann

et al. 1992

Eur J Clin Pharmacol

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“…As mentioned above, SIN-1 is the active metabolite of MOL (CorvatonÒ), a drug used for many years to treat conditions such as ischemic heart disease, angina, and pulmonary hypertension 66 . Chronic administration of MOL in rodents is well tolerated, consistent with the clinical safety profile of this drug [67][68][69][70] . Therefore, MOL was used for our in vivo experiments.…”

Section: Molsidomine Provides Neuroprotection In a Rat Model Of Vincr...supporting

confidence: 59%

Molsidomine Provides Neuroprotection Against Vincristine-induced Peripheral Neurotoxicity Through Soluble Guanylyl Cyclase Activation

Utkina-Sosunova,

Chiorazzi,

De Planell-Saguer

et al. 2024

Preprint

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Peripheral neurotoxicity is a dose-limiting adverse reaction of primary frontline chemotherapeutic agents, including vincristine. Neuropathy can be so disabling that patients drop out of potentially curative therapy, negatively impacting cancer prognosis. The hallmark of vincristine neurotoxicity is axonopathy, yet its underpinning mechanisms remain uncertain. We developed a comprehensive drug discovery platform to identify neuroprotective agents against vincristine-induced neurotoxicity. Among the hits identified, SIN-1 – an active metabolite of molsidomine – prevents vincristine-induced axonopathy in both motor and sensory neurons without compromising vincristine anticancer efficacy. Mechanistically, we found that SIN-1’s neuroprotective effect is mediated by activating soluble guanylyl cyclase. We modeled vincristine-induced peripheral neurotoxicity in rats to determine molsidomine therapeutic potential in vivo. Vincristine administration induced severe nerve damage and mechanical hypersensitivity that were attenuated by concomitant treatment with molsidomine. This study provides evidence of the neuroprotective properties of molsidomine and warrants further investigations of this drug as a therapy for vincristine-induced peripheral neurotoxicity.

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“…Others have found a duration of action of up to 5 h post dosing [5,19,20], which, as a consequence, implies administration at least 4-5 times daily to cover the 24-h treatment cycle [19,23]. In contrast, maintained effects lasting for up to 12 h can be derived from the higher dosage of 16 mg in sustainedrelease form such that administration twice daily appears to be sufficient, which, in addition, facilitates patient compliance.…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, plasma concentrations can remain within their therapeutic range without the development of tolerance, thus rendering sydnonimines at least theoretically suitable for treating heart failure on a 24 h a day basis. Since, however, the duration of action of molsidomine is only about 5 hours [5,19,20] the drug requires administration at least 4 times daily. Accordingly, it was the aim of the present study to compare the extent and duration of the haemodynamic effects of a standard regimen of molsidomine consisting of 4 rag-tablets given 6 h apart and one tablet of 16 mg in sustained-release form administered to patients with chronic congestive heart failure and to assess the dose-dependent impact of molsidomine on parameters of pulmonary as well as systemic circulation.…”

mentioning

confidence: 99%

Haemodynamic evaluation of two regimens of molsidomine in patients with chronic congestive heart failure

Lehmann

Reiniger

Beyerle

et al. 1995

Eur J Clin Pharmacol

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We investigated the extent and duration of the haemodynamic effects of two regimens of molsidomine, i.e. two tablets of a standard regimen consisting of 4 mg given 6 h apart and one tablet of 16 mg in sustained-release form once daily in 13 patients with chronic congestive heart failure using a placebo-controlled, randomized, double-blind and crossover protocol over a period of 12 h. Both regimens significantly affected systolic, mean and diastolic pulmonary arterial pressure (reductions of up to 15%), right atrial pressure (reductions of up to 35%) and total pulmonary resistance (reductions of up to 18%). The lower dose achieved its maximum action after about 1 h and remained effective for 2 h, whereas the higher dose in sustained-release form showed maximal efficacy at 2 h and remained active even at 12 h. In contrast, only minor changes in arterial blood pressure, systemic vascular resistance and cardiac output were observed on both regimens, almost exclusively at 2 h. Heart rate was not affected by either of the regimens tested. Neither regimen led to any untoward adverse effects. Thus, molsidomine is a potent vasodilating agent which, apart from its effects on preload, also acts on pulmonary arterial and right atrial pressures, leaving systemic circulation largely unaffected on the regimens tested. Administered on its own, it is therefore suitable for treatment of congestive heart failure.

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Pharmacokinetics of molsidomine in humans

Cited by 15 publications

References 2 publications

Pharmacokinetic profile of a novel slow release preparation of molsidomine

Pharmacokinetic profile of a novel slow release preparation of molsidomine

Molsidomine Provides Neuroprotection Against Vincristine-induced Peripheral Neurotoxicity Through Soluble Guanylyl Cyclase Activation

Haemodynamic evaluation of two regimens of molsidomine in patients with chronic congestive heart failure

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