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

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Aguirre C, Troconiz IF, Valdivieso A, Jimenez RM, Gonzalez JP, Calvo R, Rodriguez-Sasiain JM

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

Res Commun Mol Pathol Pharmacol. 1996 Apr;92(1):53-72.

PubMed ID

8733828 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Carriers

Drug	Carrier	Kind	Organism	Pharmacological Action	Actions
Penbutolol	Alpha-1-acid glycoprotein 1	Protein	Humans	Unknown	Other/unknown	Details