Phosphodiesterase-5 Inhibitor Therapy
Differences in clinical pharmacology of the currently marketed phosphodiesterase (PDE)5 inhibitors sildenafil, vardenafil and tadalafil are largely determined by their pharmacokinetic (PK) properties and their PDE5 inhibitory activity profile. This review outlines the basic concepts of pharmacokinetics and pharmacokinetic pharmacodynamic (PK/PD) relationships and their relevance to dose selection and applied pharmacotherapy. It is followed by a detailed comparative discussion on the pharmacokinetics and exposure-response relationship of the currently available PDE5 inhibitors, including known drug-drug interactions and dosage adjustments in special populations. The review is aimed at providing a critical assessment of the pharmacokinetics of PDE5 inhibitors, which may assist clinicians in tailoring drug and/or treatment regimens to the unique needs of each individual patient with erectile dysfunction.

Pharmacotherapy with the three Food and Drug Administration (FDA)-approved phosphodiesterase (PDE)5 inhibitors, sildenafil, vardenafil, and tadalafil, is currently the mainstay of treatment for erectile dysfunction (ED). These three PDE5 inhibitors share the same mechanism of action, but there are noted pharmacodynamic (PD) differences between the compounds regarding their selectivity and specificity for PDE inhibition with consequences predominantly for their safety profile, as well as biopharmaceutic and pharmacokinetic (PK) disparities that largely affect their efficacy profiles. As more PDE5 inhibitors become available, clinicians are increasingly being asked to differentiate among these alternative treatment options in their therapeutic recommendations, but have also the opportunity to individualize therapy with PDE5 inhibitors to meet the medical and lifestyle needs of the individual patient. Knowledge of the PK and PD properties of these compounds is imperative for understanding their clinical pharmacology and provides the basis for a rationale, scientifically based pharmacotherapy. Thus, the present article reviews basic principles in clinical pharmacology with focus on pharmacokinetics and exposure-response relationships and subsequently discusses the relevance of these concepts for the pharmacotherapy with currently available PDE5 inhibitors.