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Specific Pharmacokinetic Aspects of the Urinary Tract

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Book cover Urinary Tract

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 2011))

Abstract

This chapter reviews the evidence for “specific” pharmacokinetics playing a role in currently marketed drugs intended to treat lower urinary tract (LUT) symptoms. Principles of drug targeting include intrinsic properties of drugs or organs as well as drug formulations to modify drug release or to create confinement of drug presence. Prodrugs and specific formulations to deliver high drug concentrations at the site(s) of action as well as other ways to manipulate drug distribution to achieve enrichment in target tissues are considered. In overactive bladder (OAB), specific formulations for oxybutynin have been introduced to reduce the level of side effects of the active drug. Extended release tablet formulations and a topical gel formulation have been introduced, with efficacy similar to immediate release (IR) tablets, but with a reduction in anticholinergic adverse effects. However, these modifications have not led to outstanding performance parameters compared to other anticholinergic drugs marketed as IR formulations. Urinary excretion is discussed as potential mechanism for targeting LUT symptoms, but no strong indications appear to exist that this mechanism would contribute for currently available drugs. Intravesical administration of drugs is not a preferred option and only considered for drugs like botulinum toxin, where the inconvenient application compensates for a reasonable degree of long-term efficacy in severe refractory OAB. Alpha acid glycoprotein binding is discussed as a potential factor to influence drug tissue distribution, and it is concluded that there is reasonable evidence that for tamsulosin this mechanism is responsible for the difference in free fraction of the drug observed in plasma and prostate, which could contribute to its relative absence of blood pressure effects in patients with LUT symptoms related to benign prostate hyperplasia (LUTS-BPH). The principle of irreversible inhibition of type II 5α-reductase as a tool to develop drugs to reduce prostatic levels of dihydrotestosterone is employed by both dutasteride and finasteride for treatment of LUTS-BPH. Of the mechanisms discussed, the principles employed for the 5α-reductase blockers and tamsulosin in this respect can be considered relatively specific for its urological indication.

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Authors and Affiliations

  1. Translational and Development Pharmacology Department, Astellas Pharma Europe R&D, 108, 2350 AC, Leiderdorp, The Netherlands

    Cees Korstanje

  2. Pharmacokinetics and Modelling and Simulation Department, Astellas Pharma Europe, Leiderdorp, The Netherlands

    Walter Krauwinkel

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  1. Cees Korstanje
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  2. Walter Krauwinkel
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Correspondence to Cees Korstanje .

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Editors and Affiliations

  1. Wake Forest University, Medical Center Blvd., Winston-Salem, 27157-1088, North Carolina, USA

    Karl-Erik Andersson

  2. Academic Medical Center, Dept. Pharmacology & Pharmacotherapy, University of Amsterdam, Meibergdreef 15, Amsterdam, 1105 AZ, Netherlands

    Martin C. Michel

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Korstanje, C., Krauwinkel, W. (2011). Specific Pharmacokinetic Aspects of the Urinary Tract. In: Andersson, KE., Michel, M. (eds) Urinary Tract. Handbook of Experimental Pharmacology, vol 2011. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-16499-6_13

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