Peritoneal Dialysis Alters Tolbutamide Pharmacokinetics in Rats with Experimental Acute Renal Failure

doi:10.2133/dmpk.21.291

Drug Metabolism and Pharmacokinetics

Volume 21, Issue 4, 2006, Pages 291-296

https://doi.org/10.2133/dmpk.21.291 Get rights and content

Summary:

The plasma concentration profile of the antidiabetic agent tolbutamide was investigated in glycerol-induced acute renal failure (ARF) rats receiving or not receiving peritoneal dialysis (PD) to assess the impact of performing dialysis on tolbutamide pharmacokinetics. It was revealed that the plasma concentration of tolbutamide was decreased by 23.4% by performing PD in ARF rats, while it was not changed by PD in normal rats. The decrease in the plasma concentration of tolbutamide was nearly proportional to the increase in its volume of distribution. To clarify the mechanisms responsible for the decreased tolbutamide concentration caused by PD, the plasma protein binding of tolbutamide was examined in normal and ARF rats. The plasma unbound fraction of tolbutamide was higher in ARF rats than in normal rats, and the dissociation constants were 3.5±0.7 and 5.5±0.2 μg/mL in normal and ARF rats, respectively. These results indicated that the unbound fraction of tolbutamide was increased in ARF rats because of its protein binding being suppressed. It is therefore likely that since a measurable amount of tolbutamide can distribute in peritoneal dialysate in ARF rats, but not in normal rats, the plasma concentration of tolbutamide was decreased by performing PD only in ARF rats. These findings suggest that diabetes medication with tolbutamide should be carefully performed in patients receiving dialysis treatment.

References (27)

J. Judis
Binding of sulfonylureas to serum proteins
J. Pharm. Sci.
(1972)
A. Kabanda et al.
Factors influencing serum levels and peritoneal clearances of low molecular weight proteins in continuous ambulatory peritoneal dialysis
Kidney Int.
(1995)
R. Vanholder et al.
Protein-bound uremic solutes: the forgotten toxins
Kidney Int.
(2001)
J.C. Pechere et al.
Pharmacokinetics of intravenously administered tobramycin in normal volunteers and in renal-impaired and hemodialyzed patients
J. Infect. Dis.
(1976)
H.J. Manley et al.
Pharmacokinetics of intermittent intravenous cefazolin and tobramycin in patients treated with automated peritoneal dialysis
J. Am. Soc. Nephrol.
(2000)
H.J. Manley et al.
Intravenous vancomycin pharmacokinetics in automated peritoneal dialysis patients
Perit. Dial. Int.
(2001)
D.A. Sica et al.
Pharmacokinetics and blood pressure response of losartan in end-stage renal disease
Clin. Pharmacokinet.
(2000)
S. Kishino et al.
Influence of continuous venovenous haemodiafiltration on the pharmacokinetics of tacrolimus in liver transplant recipients with small-for-size grafts
Clin. Transplant.
(2003)
D.D. Christ
Human plasma protein binding of the angiotensin II receptor antagonist losartan potassium (DuP 753/MK 954) and its pharmacologically active metabolite EXP3174
J. Clin. Pharmacol.
(1995)
K. Nagase et al.
Distribution and protein binding of FK506, a potent im-munosuppressive macrolide lactone, in human blood and its uptake by erythrocytes
J. Pharm. Pharmacol.
(1994)

L.Z. Benet et al.

Design and optimization of dosage regimens; pharmacokinetic data

J.J. Thiessen et al.

Plasma protein binding of diazepam and tolbutamide in chronic alcoholics

J. Clin. Pharmacol.

(1976)

H. Katayama et al.

Effect of acute renal failure on the disposition of cefoperazone

J. Pharm. Pharmacol.

(1999)

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The aim of this study was to present a deductive compartment pharmacokinetic (PK) model to predict the concentration profiles of drugs in plasma and peritoneal fluid in peritoneal dialysis (PD) rats. PK parameters of model drugs in normal and experimentally induced acute renal failure (ARF) rats not undergoing PD were obtained inductively in a common regression manner with a two-compartment model. In PD normal and ARF rats, PK parameters relating to the transfer of drugs to the peritoneal dialysate and the progress of renal failure were deductively modified to simulate the drug concentration-time profiles in plasma and in the peritoneal fluid in PD rats. The deductively introduced modifiers were the volume of distribution in the peripheral compartment, plasma protein binding, and solvent movement factor to the peritoneal fluid. Predicted profiles of tolbutamide, propranolol and cefazolin in PD normal and ARF rats were compared with the corresponding observed data. This minimal deductive approach yielded satisfactory accuracy in the prediction of both the plasma and peritoneal fluid concentrations of tolbutamide and propranolol.
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Regular ArticlePeritoneal Dialysis Alters Tolbutamide Pharmacokinetics in Rats with Experimental Acute Renal Failure

Summary:

J. Pharm. Sci.

Kidney Int.

Kidney Int.

Pharmacokinetics of intravenously administered tobramycin in normal volunteers and in renal-impaired and hemodialyzed patients

J. Infect. Dis.

Pharmacokinetics of intermittent intravenous cefazolin and tobramycin in patients treated with automated peritoneal dialysis

J. Am. Soc. Nephrol.

Intravenous vancomycin pharmacokinetics in automated peritoneal dialysis patients

Perit. Dial. Int.

Pharmacokinetics and blood pressure response of losartan in end-stage renal disease

Clin. Pharmacokinet.

Influence of continuous venovenous haemodiafiltration on the pharmacokinetics of tacrolimus in liver transplant recipients with small-for-size grafts

Clin. Transplant.

Human plasma protein binding of the angiotensin II receptor antagonist losartan potassium (DuP 753/MK 954) and its pharmacologically active metabolite EXP3174

J. Clin. Pharmacol.

Distribution and protein binding of FK506, a potent im-munosuppressive macrolide lactone, in human blood and its uptake by erythrocytes

J. Pharm. Pharmacol.

Design and optimization of dosage regimens; pharmacokinetic data

Plasma protein binding of diazepam and tolbutamide in chronic alcoholics

J. Clin. Pharmacol.

Effect of acute renal failure on the disposition of cefoperazone

J. Pharm. Pharmacol.

Regular Article
Peritoneal Dialysis Alters Tolbutamide Pharmacokinetics in Rats with Experimental Acute Renal Failure