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Tadalafil population pharmacokinetics in patients with erectile dysfunction

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

The purpose of this study was to characterize pharmacokinetics of tadalafil (Cialis) and potential sources of variability in patients with erectile dysfunction (ED).

Methods

Population models were developed to describe tadalafil pharmacokinetics in 227 patients with mild to severe ED in a phase III trial. Parallel groups of patients received 2, 5, or 10 mg tadalafil or placebo orally, as needed, for 12 weeks.

Results

Tadalafil pharmacokinetics in patients with ED were linear with respect to dose and duration of treatment, and a one-compartment model adequately described the data. The absorption rate was rapid (1.86 h−1), and the typical population estimates of the apparent oral clearance (CL/F) and apparent volume of distribution were 1.6 l/h and 63.8 l, respectively. Disposition parameters showed a moderate degree of interindividual variability (39–45%). The value of CL/F decreased slightly with increasing serum γ-glutamyl transferase (GGT) concentration, the only statistically significant covariate detected. Systemic exposure to tadalafil was not influenced by age, weight, smoking status, alcohol consumption, liver enzyme status, ED severity, cardiovascular condition, or diabetes mellitus.

Conclusion

Pharmacokinetics in the efficacy/safety trial population are essentially similar to pharmacokinetics in healthy subjects, and no patient-specific factor warranting clinical consideration of dose regimen adjustment was identified in these analyses.

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Acknowledgements

We are grateful for the many contributions of our former Lilly Research Centre colleagues, particularly Drs. Alison Mackie and Beverley Patterson. We thank Elizabeth Peck for analytical support and Dr. Diane Phillips for managing all analytical aspects, Karen Schneck for the power analysis of age, and Drs. Vikram Sinha and Malcolm Mitchell for their review of the manuscript.

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Correspondence to S. Thomas Forgue.

Additional information

This research was funded by Lilly ICOS LLC, Indianapolis, IN, and Bothell, WA.

Financial disclosure

Authors are present (S.T. Forgue) or previous (A. Staab, C. Tillmann) employees of Eli Lilly and Company or have received financial contractual support from this company (I. Troconiz, J. Rapado). S.T. Forgue owns stock in Eli Lilly & Company.

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Trocóniz, I.F., Tillmann, C., Staab, A. et al. Tadalafil population pharmacokinetics in patients with erectile dysfunction. Eur J Clin Pharmacol 63, 583–590 (2007). https://doi.org/10.1007/s00228-007-0297-1

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  • DOI: https://doi.org/10.1007/s00228-007-0297-1

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