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• W1564092816 abstract "The efficacy-tolerability profile of tamsulosin in patients with benign prostatic hyperplasia (BPH) is assumed to be associated both with the α1-adrenoceptor selectivity profile of the drug and a small peak : trough ratio in the plasma pharmacokinetic (PK) profile. Tamsulosin is highly bound to plasma proteins, notably α1-acid glycoprotein (AGP). This protein is a high-affinity binding protein and AGP plasma concentration was found to influence the therapeutic (unbound) plasma concentrations for high-AGP-binding drugs.The study actually assessed unbound tamsulosin concentrations in both blood plasma and prostate tissue and reported that the unbound tamsulosin concentrations after multiple dosing in men with BPH, were much higher in prostate than in blood plasma. The assumption is put forward that differential free drug concentrations in prostate and blood plasma may contribute to the relative ‘uroselectivity’ of tamsulosin.The aim of this small patient study was to investigate tamsulosin concentrations in prostate and plasma samples in order to identify potential differences in the pharmacokinetics (PK) in plasma and prostate contributing to its pharmacodynamic activity profile in patients.Forty-one patients with benign prostatic hyperplasia (BPH) scheduled for open prostatectomy were given tamsulosin 0.4 mg for 6-21 days in order to reach steady-state PK. Patients were randomized over four groups to allow collection of plasma and tissue samples at different time points after last dose administration. Samples were collected during surgery and assayed for tamsulosin HCl. The free fraction (f(u)) of tamsulosin was determined by ultracentrifugation of plasma and prostate tissue spiked with (14)C-tamsulosin.C(max) in plasma at 4.4 h for total tamsulosin was 15.2 ng ml(-1) and AUC(0,24 h) was 282 ng ml(-1) h, while for prostate C(max) at 11.4 h post-dose was 5.4 ng ml(-1) and AUC(0,24 h) was 120 ng ml(-1) h. AUC(0,24 h) for total tamsulosin in prostate was 43% of the plasma AUC(0,24 h). f(u) was 0.4 % for plasma and 59.1% for prostate. Therefore calculated on unbound tamsulosin, a ratio of 63 resulted for prostate vs. plasma C(max) concentrations.These data indicate that in patients with confirmed BPH the amount of tamsulosin freely available in the target tissue (prostate) is much higher than in plasma." @default.
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• W1564092816 date "2011-07-11" @default.
• W1564092816 modified "2023-09-25" @default.
• W1564092816 title "Tamsulosin shows a higher unbound drug fraction in human prostate than in plasma: a basis for uroselectivity?" @default.
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• W1564092816 doi "https://doi.org/10.1111/j.1365-2125.2010.03870.x" @default.
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