Unchanged protein binding of penbutolol in renal insufficiency: a possible role of carbamylation.

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Aguirre C, Calvo R, Rodriguez-Sasiain JM

Unchanged protein binding of penbutolol in renal insufficiency: a possible role of carbamylation.

Int J Clin Pharmacol Ther Toxicol. 1993 Jan;31(1):31-4.

PubMed ID

8444514 [ View in PubMed

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Abstract

The effect of in vitro carbamylation of serum protein with potassium cyanate on protein binding of penbutolol, a basic agent exclusively bound to alpha 1 acid glycoprotein (AAG), was investigated. Carbamylation of serum resulted in a weak increase on free fraction of penbutolol (4.45 +/- 0.54% before carbamylation vs 5.66 +/- 0.40% after; p < 0.025). Parallelly, potassium cyanate added to pure AAG and incubated for 90 min induced carbamylation of this protein (38 mumoles of 14C cyanate incorporated per gram of protein). A study in serum from patients with chronic renal disease (pre and postdialysis) showed no changes in protein binding of penbutolol, although AAG levels were significantly higher. However, Scatchard [1949] plot for penbutolol binding to serum from renal patients (both pre and postdialysis) showed a decrease in affinity constant (nKa = 11.13 x 10(5) M-1 in healthy volunteers, vs 5.56 x 10(5) M-1 in patients before dialysis and 4.57 x 10(5) M-1 after dialysis). We concluded that carbamylation of serum AAG in uremic patients could explain, in part, the absence of changes in protein binding of any basic drugs in this pathological condition. It appears that a decreased affinity constant could balance the effect of increased AAG levels.

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