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• W4230767056 abstract "1Pharmacokinetic 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). 2Investigations 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.] μg ml−1 h) was markedly higher than the AUC determined at steady state (13.2 [±3.8 s.d.] μg 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.] μg ml−1 h) in controls and (34.4 [±14.9 s.d.] μg 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.] μg ml−1 h) in controls and (20.8 [±6.8 s.d.] μg 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. 5An inverse correlation was seen between the results of the monoethylglycin-xilidid (MEGX)-test and the AUC of trapidil (single dose: r=−0.516, P=0.048; steady state: r=−0.548, P=0.042). 6Results 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." @default.
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• W4230767056 date "1996-10-01" @default.
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• W4230767056 title "Pharmacokinetics of trapidil, an antagonist of platelet derived growth factor, in healthy subjects and in patients with liver cirrhosis" @default.
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• W4230767056 doi "https://doi.org/10.1111/j.1365-2125.1996.tb00006.x" @default.
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