Effect of unilateral nephrectomy on the pharmacokinetics of atenolol in humans.
Unilateral nephrectomy is a common surgical procedure and involves functional adaptation of the remaining kidney. There is a paucity of data addressing whether drugs eliminated predominantly through the urinary tract, such as atenolol, can be effectively handled by unilaterally nephrectomized patients. This study was carried out in 28 subjects 1 month (10 subjects) and 1 year (10 subjects) after unilateral nephrectomy, as well as in 8 healthy volunteers who were administered atenolol as a single oral dose of 100 mg. Pharmacokinetic parameters of atenolol were calculated using a one-compartment open model. It was revealed that atenolol blood serum concentrations were significantly elevated in nephrectomized patients as compared with the control subjects, especially 1 month after the surgery. Patients nephrectomized 1 month prior to the study were characterized by an increase in AUC by 43% (p < 0.05), reduction of lambda z by 36% (p < 0.001) and CLT by 27% (p < 0.001), and prolongation of t1/2 by 60% (p < 0.001) in comparison with healthy volunteers. The values of atenolol pharmacokinetic parameters in patients 1 year after unilateral nephrectomy did not differ significantly as compared to the controls. However, a trend indicating an impaired elimination was noted. A decrease in lambda z by 16%, prolongation of t1/2 by 32%, and reduction of CLT by 32% were observed. The results suggest that unilateral nephrectomy impairs elimination of atenolol and possibly other drugs predominantly eliminated via the kidney.
Department of Experimental and Clinical Pharmacology, Pomeranian Academy of Medicine, Powstancow Wlkp. 72, 70-111 Szczecin, Poland.
Marek
M
Drozdzik
Leszek
L
Domanski
Jerzy
J
Wojcicki
Artur
A
Pudlo
Piotr
P
Machoy
D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics*; D000328:Adult; D000375:Aging / Q000378:metabolism; D019540:Area Under Curve; D001262:Atenolol / Q000493:pharmacokinetics*; D001835:Body Weight / Q000502:physiology; D005260:Female; D006207:Half-Life; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D009392:Nephrectomy / Q000009:adverse effects*
D000319:Adrenergic beta-Antagonists; D001262:Atenolol