ALLEN D. SEFTEL, M.D.

Dept. of Urology and Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA 

Phosphodiesterase Type 5 Inhibitors: Pharmacokinetic Properties

Results of pharmacokinetic studies have shown that there are important differences in the absorption and elimination characteristics with the PDE5 inhibitors. Peak plasma concentrations, or C_max, may be related to the therapeutic response to a particular drug. Among the variables that can affect C_max are the presence of concomitant medications or ingestion of food.1

Administration of sildenafil with a high-fat meal reduces the Cmax by about 29% (Table I) and delays the time to achieve peak plasma concentration, or Tmax, by about 1 h.

Clinically, this may result in a delayed onset of action for sildenafil. This drug/food interaction is one of the likely causes for treatment failure of sildenafil in men who are unaware that this medication should be administered on an empty stomach for optimal efficacy. Similarly, taking vardenafil with a high- fat meal decreases the C_max ranging from 18 to 50% and de- lays T_max by about 1 h (Fig. 2).3 

High-fat breakfast moderately reduces Cmax by about 18% and delays Tmax by about 1 h.

FIG. 2  The effect of food on vardenafil pharmacokinetics. After consumption of a high-fat breakfast, Cmax decreased and median tmax increased. The median tmax was 1h under fasting conditions and 2h after consumption of a high-fat meal.

Both the rate and extent of absorption of tadalafil are unaffected by the presence of high-fat food and, therefore, this medication can be taken with or without food (Fig. 3).2, 4

FIG. 3  The effect of food on tadalafil pharmacokinetics. Consumption of a high-fat meal has no clinically relevant effect on the rate and extent of tadalafil absorption in the body. Therefore, tadalafil can be administered without regard to food.

Conclusions

In response to sexual stimulation, PDE5 inhibitors enhance vasodilation and relaxation of the penile vascular smooth muscle, resulting in improved erectile function. The PDE5 inhibitors (i.e., sildenafil, tadalafil, and vardenafil) are highly selective for the PDE5 isoenzyme.

A important pharmacokinetic difference among the PDE5 inhibitors involves the effects on absorption of these agents when administered in the presence of high-fat food. Reports of decreased plasma concentrations and delayed absorption have been associated with sildenafil and vardenafil, potentially resulting in a slower onset of action or reduced efficacy. However, similar effects have not been observed with tadalafil when administered with high-fat food.

References

1. Corbin JD, Francis SH: Pharmacology of phosphodiesterase-5 in- Int J Clin Pract 2002;56:453–459
2. Padma-Nathan H, Giuliano F: Oral drug therapy for erectile dys- Urol Clin North Am 2001;28:321–334
3. Rajagopalan P, Mazzu A, Xia C, Dawkins R, Sundaresan P: Effect of a high-fat breakfast and moderate-fat evening meal on the phar- macokinetics of vardenafil, an oral phosphodiesterase-5 inhibitor for the treatment of erectile J Clin Pharmacol 2003; 43:260–267
4. Patterson B, Bedding A, Jewell H, Payne C, Mitchell M: The effect of intrinsic and extrinsic factors on the pharmacokinetic properties of tadalafil (IC351). Poster presented at 4th Congress of the European Society for Sexual and Impotence Research, Rome, Italy, September 30–October 3, 2001

From the study “Phosphodiesterase Type 5 Inhibitor Differentiation Based on Selectivity, Pharmacokinetic, and Efficacy Profiles”

 (Source from: https://www.ncbi.nlm.nih.gov/pubmed/15115191)