Pharmacokinetics and pharmacodynamics of penbutolol in healthy and cancer subjects: role of altered protein binding.

Abstract

The pharmacokinetic and pharmacodynamic profiles of penbutolol were examined in healthy volunteers and in cancer patients using a pharmacokinetic/pharmacodynamic (pk/pd) model. After receiving a 40 mg single oral dose of penbutolol, the absorption rate constant, apparent volume of distribution and serum clearance of penbutolol were found to be reduced in the cancer group. Changes in the disposition of the conjugate metabolite were also observed in the cancer patients. Penbutolol unbound fraction in serum was statistically decreased (p < 0.005) in the cancer group, according to the increase in the serum levels of alpha 1-acid glycoprotein seen in that group (p < 0.05). The pharmacodynamic effect of penbutolol was measured as the reduction in heart rate (HR); in healthy volunteers, a linear relationship (p < 0.01) between effect and penbutolol serum concentrations (total or unbound) was found. In contrast, in cancer patients, values of HR did not vary statistically in respect to baseline values. These results show that in cancer patients, a change in the pharmacokinetics of penbutolol occurs (associated with changes in drug protein binding), together with an alteration in the pharmacodynamics.

• Authors: C Aguirre, I F Trocóniz, A Valdivieso, R M Jiménez, J P González, R Calvo, J M Rodríguez-Sasiaín
• Journal: Research communications in molecular pathology and pharmacology (Res Commun Mol Pathol Pharmacol) Vol. 92 Issue 1 Pg. 53-72 (Apr 1996) ISSN: 1078-0297 [Print] United States
• PMID: 8733828 (Publication Type: Journal Article)

Chemical References

• Penbutolol

Topics

• Adult
• Aged
• Binding, Competitive
• Gastrointestinal Neoplasms (metabolism)
• Humans
• Male
• Middle Aged
• Penbutolol (pharmacokinetics, pharmacology)
• Protein Binding (physiology)