Pharmacokinetic profile of a novel slow release preparation of molsidomine

Rietbrock, Stephan; Keller‐Stanislawski, Brigitte; Thürmann, Petra A.; Brockmeier, D.

doi:10.1007/bf02333022

Cited by 6 publications

(1 citation statement)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is a very useful tool to decipher the atypical absorption profiles. Some drugs, such as cimetidine, molsidomine, 106 colchicine, 107 and dipyridamole, can exhibit significant double‐peak or multiple‐peak phenomena following oral dosing. Many potential causes could attribute to those phenomena.…”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetic Strategies in Deciphering Atypical Drug Absorption Profiles

Zhou¹

2003

The Journal of Clinical Pharma

123

View full text Add to dashboard Cite

Drug absorption is a very complex process that manifests itself through potential interaction with a host of physicochemical and physiological variables. Some factors that may affect the absorption processes include presystemic metabolism/efflux, the "absorption window" along the gastrointestinal tract, disease states, demographics (gender, age, ethnicity), and biopharmaceutical classification of solid dosage forms. Despite the complexity of the absorption processes, the analysis of the absorption kinetic data is mostly empirical, and the assumption of first-order absorption is axiomatic. Nevertheless, we often encounter irregular drug absorption profiles (such as double-peak, absorption window-type absorption profiles, etc.) that cannot be satisfactorily described by a simple first-order absorption process. The selection of an inappropriate absorption model would result in the misspecification of the pharmacokinetic model and subsequent erroneous prediction of the dosing regimen. This article presents several pharmacokinetic strategies in analyzing typical and atypical absorption profiles. The atypical absorption profiles discussed in this article include parallel first-order absorption, mixed zero-order and first-order absorption, Weibull-type absorption, absorption window with or without Michaelis-Menton absorption, time-dependent absorption, and inverse Gaussian density absorption. In any event, intravenous drug concentration-time data are generally needed to avoid the ambiguousness in the absorption analyses.

show abstract

Section: Resultsmentioning

confidence: 99%

Pharmacokinetic Strategies in Deciphering Atypical Drug Absorption Profiles

Zhou¹

2003

The Journal of Clinical Pharma

123

View full text Add to dashboard Cite

show abstract

Efficacy and safety of once- and twice-daily formulations of molsidomine in patients with stable angina pectoris: Double-blind and open-label studies

et al. 2006

View full text Add to dashboard Cite

Molsidomine, a sydnonimine acting as a heterocyclic direct nitric oxide donor, has been used for many years in several European countries for the treatment of patients with stable angina pectoris. The efficacy and tolerability of a novel once-daily 16-mg formulation of molsidomine (M16) were compared with those of the currently used twice-daily 8-mg molsidomine tablet (M8) in 666 patients. Study 1, a multicenter, randomized, double-blind, placebo-controlled, twin crossover study, involved 533 patients given acute and 2-week treatment with each drug formulation. Study 2, a multicenter, open-label, sequential, add-on trial, compared M16 and M8 in 133 patients. Drug effects on exercise capacity (study 1 only), frequency of anginal attacks and consumption of short-acting itroderivatives, and incidence of adverse events (AEs) were evaluated. Compared with placebo, M16 increased exercise capacity by 15% (P<.001) at the start of study 1 and by 13% (P<.001) after 2 weeks' treatment, and was not inferior to M8. In terms of anginal attack frequency and nitroderivative consumption, M16 was not inferior to M8 in either study. Moreover, compared with M8, M16 produced a statistically and clinically significant reduction in the incidence of anginal attacks in elderly (>/=75 y) but not in younger patients (<75 y) (study 2), nor in patients from study 1. No significant difference from M8 was found in either study in short-acting nitroderivative consumption. No tolerance to M8 or M16 was observed after 2-week treatment. No statistically significant differences in incidences of all AEs and drug-related AEs were observed between M16 and M8 in either study. The same held true for proportions of patients experiencing AEs and drug-related AEs on M16 vs M8: in study 1-14.3% and 11.8% for all AEs (P=.218), 6.9% and 5.4% for drug-related AEs (P=.280); in study 2-1.3% and 1.3% for all AEs, 0% and 1.3% for drug-related AEs (P>.10) in young patients; and in the elderly, 3.6% and 0% for drug-related AEs (P>.10). Only the proportion of elderly patients with all AEs was significantly higher with M16 than with M8: 14.5% vs 1.8% (P=.039). M16 once daily was effective and well tolerated in investigated patients with stable angina pectoris, particularly the elderly, affording 24 hours of therapeutic activity. M16 was not inferior to M8 given twice daily in terms of efficacy, safety profile, and tolerability.

show abstract