English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

1. Pharmacokinetic parameters of trapidil (an antagonist of platelet derived growth factor) were evaluated in 12 healthy male subjects (study I) and in a group of 10 patients with liver cirrhosis (Child B) and five control subjects, respectively (study II). 2. Investigations were carried out after a single dose trapidil (200 mg) and at steady state after application of 200 mg trapidil three times daily for 5 days (study 1) or 4 days (study II). 3. Study I: The concentration-time curves of the terminal elimination phase of trapidil exhibited a slight convexity which might reflect nonlinear kinetics. The AUC of trapidil obtained after the first dose (20.5 [+/- 7.0 s.d.] micrograms ml-1 h) was markedly higher than the AUC determined at steady state (13.2 [+/- 3.8 s.d.] micrograms ml-1 h), the non-parametric 90% confidence intervals of the ratio day 5/day 1 was 0.58-0.73 (point estimator 0.64). 4. Study II: AUC averaged (21.4 [+/- 9.1 s.d.] micrograms ml-1 h) in controls and (34.4 [+/- 14.9 s.d.] micrograms ml-1 h) in cirrhotic patients. The 90% confidence intervals for the difference group 1 vs group 2 was 0.95-2.97 (point estimator 1.48, P = 0.066). At steady state, AUC averaged (13.7 [+/- 5.7 s.d.] micrograms ml-1 h) in controls and (20.8 [+/- 6.8 s.d.] micrograms ml-1 h) in cirrhotic patients (90% confidence intervals group 1 vs group 2: 0.88-2.20 [point estimator 1.45, P = 0.05]). As seen in study I, the AUC of trapidil obtained after the first dose was markedly higher than the AUC determined at steady state, the non-parametric 90% confidence intervals of the ratio day 5/day 1 was 0.48-0.84 (point estimator 0.66) in control subjects and 0.54-0.72 (point estimator 0.64) in cirrhotic patients, respectively. 5. An inverse correlation was seen between the results of the monoethylglycinxilidid (MEGX)-test and the AUC of trapidil (single dose: r = -0.516, P = 0.048; steady state: r = -0.548, P = 0.042). 6. Results of study I and study II indicate an autoinduction of trapidil metabolism after repeated oral doses. Although trapidil elimination is decreased in patients with liver cirrhosis (study II), the elimination half-life at steady state is relatively short (2.4 [+/- 1.1 s.d.] h) and therefore should prevent cumulation of trapidil even in cirrhotic patients.

Pharmacokinetics of trapidil, an antagonist of platelet derived growth factor, in healthy subjects and in patients with liver cirrhosis