Pharmacology of phosphodiesterase-5 inhibitors

Int J Clin Pract. Jul-Aug 2002;56(6):453-9.

Abstract

The clinical properties (efficacy and safety profile) of a medicine are related not only to its mode of action, but also to its selectivity for its target (usually a receptor or enzyme) and are also influenced by its pharmacokinetic properties (absorption, distribution, metabolism and elimination). The growing number of phosphodiesterase inhibitors that are selective for phosphodiesterase-5 (PDE5) represent a promising new class of compounds that are useful for the treatment of erectile dysfunction and perhaps other disorders. Some of the basic pharmacodynamic and pharmacokinetic parameters that describe drug action are discussed with regard to the new PDE5 inhibitors. Central topics reviewed are the concentration that produces a given in vitro response, or potency (IC50), maximum plasma concentration (Cmax), time to Cmax (Tmax), half-life (t 1/2), area under the curve (AUC), bioavailability, onset and duration of action, and the balance to achieve optimum safety and efficacy. To illustrate these concepts, a group of inhibitors with varying selectivities and potencies for PDE5 (theophylline, IBMX, zaprinast, sildenafil, tadalafil and vardenafil) are discussed. Each drug has its own set of unique pharmacological characteristics based on its specific molecular structure, enzyme inhibition profile and pharmacokinetic properties. Each PDE5 inhibitor has a distinct selectivity that contributes to its safety profile. As with all new drugs, and especially those in a new class, careful evaluation will be necessary to ensure the optimal use of the PDE5 inhibitors.

Publication types

  • Review

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacokinetics
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Area Under Curve
  • Carbolines
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Erectile Dysfunction / drug therapy
  • Humans
  • Imidazoles / pharmacokinetics
  • Imidazoles / therapeutic use
  • Male
  • Muscle, Smooth, Vascular / drug effects
  • Phosphodiesterase Inhibitors / pharmacokinetics*
  • Phosphodiesterase Inhibitors / therapeutic use
  • Phosphoric Diester Hydrolases*
  • Piperazines / pharmacokinetics
  • Piperazines / therapeutic use
  • Purines
  • Purinones / pharmacokinetics
  • Purinones / therapeutic use
  • Sildenafil Citrate
  • Sulfones
  • Tadalafil
  • Theophylline / pharmacokinetics
  • Triazines
  • Vardenafil Dihydrochloride

Substances

  • Carbolines
  • Imidazoles
  • Phosphodiesterase Inhibitors
  • Piperazines
  • Purines
  • Purinones
  • Sulfones
  • Triazines
  • Vardenafil Dihydrochloride
  • Tadalafil
  • Sildenafil Citrate
  • Theophylline
  • Phosphoric Diester Hydrolases
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • PDE5A protein, human
  • zaprinast
  • 1-Methyl-3-isobutylxanthine