ArticlePharmaceutical research2009
Mechanism-based pharmacokinetic-pharmacodynamic modeling of bidirectional effect of danshensu on plasma homocysteine in rats.
Article in Pharmaceutical research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 11 citations in OpenAlex.
- Integrative population pharmacokinetic/pharmacodynamic analysis of nemonoxacin capsule in Chinese patients with community-acquired pneumonia.Frontiers in pharmacology · 2023Article
- Combined PK/PD Index May Be a More Appropriate PK/PD Index for Cefoperazone/Sulbactam againstAntibiotics (Basel, Switzerland) · 2022Article
- Pharmacokinetics and pharmacodynamics of levofloxacin in bronchial mucosa and lung tissue of patients undergoing pulmonary operation.Experimental and therapeutic medicine · 2020Article
- Dose Optimization of Colistin Combinations against Carbapenem-Resistant Acinetobacter baumannii from Patients with Hospital-Acquired Pneumonia in China by Using anAntimicrobial agents and chemotherapy · 2019Article
- Modeling Disease Progression: Angiotensin II Indirectly Inhibits Nitric Oxide Production via ADMA Accumulation in Spontaneously Hypertensive Rats.Frontiers in physiology · 2016Article
- The pharmacokinetic-pharmacodynamic model of azithromycin for lipopolysaccharide-induced depressive-like behavior in mice.PloS one · 2013Article
- Cellular pharmacokinetic mechanisms of adriamycin resistance and its modulation by 20(S)-ginsenoside Rh2 in MCF-7/Adr cells.British journal of pharmacology · 2012Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo develop a mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) model to characterize and predict the bidirectional effect of danshensu on plasma total homocysteine (tHcy) in rats described in our previous paper.
methodsThe effect of danshensu on tHcy was assessed in rats after simultaneously methionine loading. Danshensu, its methylated metabolite and tHcy were all quantified after single intravenous injection of 20 mg/kg danshensu. The bidirectional effect, of which, elevated by danshensu methylation and decreased via transsulfuration promotion, was characterized by a PK-PD model, where direct stimulatory sigmoidal function and time-dependent transduction function were introduced for the two effects description, respectively.
resultsModeling and simulations reveals that: (1) the elevated effect by methylation occurs before the decreased effect via transsulfuration promotion, and the decreased effect is more profoundly dose-dependent than the elevated effect; (2) two steps are simplified to describe the delayed stimulatory effect on the transsulfuration in the model; (3) long term administration of danshensu dose not affect tHcy in normal rats, while it significantly reduces tHcy in rats treated with methionine. This is in consistent with previous report.
conclusionsThe profiles were well-described by our PK-PD model, which constitutes a basis for the future development of mechanism-based model for polyphenols on Hcy in this paradigm.
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