Diazepam and lidocaine plasma protein binding in renal disease

Steven H. Grossman, Dwight Davis, Barbara B. Kitchell, David G. Shand, Philip A. Routledge

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Abstract

The plasma protein binding of diazepam and lidocaine was measured in patients with renal disease (those with uremia, nephrotic syndrome, or who had received a transplant) and in age- and sex-matched control subjects. Percentage unbound diazepami in plasma was increased over control in all three groups of patients as follows: uremic patients 3.23%, control, 1.64% (P < 0.001), nephrotic patients, 3.55%, control, 1.63% (P < 0.001); and transplant recipients, 2.11 %, control 1.50% (P < 0.001). The binding ratio (molar concentration of bound to unbound drug) in the patients was related to albumin concentration (r = 0.609, P < 0.001). Percentage of unbound lidocaine did not differ substantially from control in nephrotic patients (34.2%, control 30.8%a), but was reduced in the uremic patients (20.8%, control 30.7%, P < 0.001) and transplant recipients (24.6%, control 33.7%, P < 0.005). These increases were associated with increases in al-acid glycoprotein (AAG) concentration (uremic patients 134.9 mg/dl, control 66.3, P < 0.001; transplant recipients 106.5, control 65.6, P < 0.001). The binding ratio of lidocaine was closely related to the AAG concentration in patients (r = 0.933, P < 0.001) and controls (r = 0.719, P < 0.001). Thus, the binding of basic drugs may be increased or decreased in patients with renal disease, depending on the relative contribution of the individual plasma proteins to the total binding and the type of disease.

Original languageEnglish (US)
Pages (from-to)350-357
Number of pages8
JournalClinical Pharmacology and Therapeutics
Volume31
Issue number3
DOIs
StatePublished - Jan 1 1982

Fingerprint

Diazepam
Lidocaine
Protein Binding
Blood Proteins
Kidney
Glycoproteins
Acids
Uremia
Nephrotic Syndrome
Pharmaceutical Preparations
Albumins
Transplants

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Grossman, Steven H. ; Davis, Dwight ; Kitchell, Barbara B. ; Shand, David G. ; Routledge, Philip A. / Diazepam and lidocaine plasma protein binding in renal disease. In: Clinical Pharmacology and Therapeutics. 1982 ; Vol. 31, No. 3. pp. 350-357.
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abstract = "The plasma protein binding of diazepam and lidocaine was measured in patients with renal disease (those with uremia, nephrotic syndrome, or who had received a transplant) and in age- and sex-matched control subjects. Percentage unbound diazepami in plasma was increased over control in all three groups of patients as follows: uremic patients 3.23{\%}, control, 1.64{\%} (P < 0.001), nephrotic patients, 3.55{\%}, control, 1.63{\%} (P < 0.001); and transplant recipients, 2.11 {\%}, control 1.50{\%} (P < 0.001). The binding ratio (molar concentration of bound to unbound drug) in the patients was related to albumin concentration (r = 0.609, P < 0.001). Percentage of unbound lidocaine did not differ substantially from control in nephrotic patients (34.2{\%}, control 30.8{\%}a), but was reduced in the uremic patients (20.8{\%}, control 30.7{\%}, P < 0.001) and transplant recipients (24.6{\%}, control 33.7{\%}, P < 0.005). These increases were associated with increases in al-acid glycoprotein (AAG) concentration (uremic patients 134.9 mg/dl, control 66.3, P < 0.001; transplant recipients 106.5, control 65.6, P < 0.001). The binding ratio of lidocaine was closely related to the AAG concentration in patients (r = 0.933, P < 0.001) and controls (r = 0.719, P < 0.001). Thus, the binding of basic drugs may be increased or decreased in patients with renal disease, depending on the relative contribution of the individual plasma proteins to the total binding and the type of disease.",
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Diazepam and lidocaine plasma protein binding in renal disease. / Grossman, Steven H.; Davis, Dwight; Kitchell, Barbara B.; Shand, David G.; Routledge, Philip A.

In: Clinical Pharmacology and Therapeutics, Vol. 31, No. 3, 01.01.1982, p. 350-357.

Research output: Contribution to journalArticle

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N2 - The plasma protein binding of diazepam and lidocaine was measured in patients with renal disease (those with uremia, nephrotic syndrome, or who had received a transplant) and in age- and sex-matched control subjects. Percentage unbound diazepami in plasma was increased over control in all three groups of patients as follows: uremic patients 3.23%, control, 1.64% (P < 0.001), nephrotic patients, 3.55%, control, 1.63% (P < 0.001); and transplant recipients, 2.11 %, control 1.50% (P < 0.001). The binding ratio (molar concentration of bound to unbound drug) in the patients was related to albumin concentration (r = 0.609, P < 0.001). Percentage of unbound lidocaine did not differ substantially from control in nephrotic patients (34.2%, control 30.8%a), but was reduced in the uremic patients (20.8%, control 30.7%, P < 0.001) and transplant recipients (24.6%, control 33.7%, P < 0.005). These increases were associated with increases in al-acid glycoprotein (AAG) concentration (uremic patients 134.9 mg/dl, control 66.3, P < 0.001; transplant recipients 106.5, control 65.6, P < 0.001). The binding ratio of lidocaine was closely related to the AAG concentration in patients (r = 0.933, P < 0.001) and controls (r = 0.719, P < 0.001). Thus, the binding of basic drugs may be increased or decreased in patients with renal disease, depending on the relative contribution of the individual plasma proteins to the total binding and the type of disease.

AB - The plasma protein binding of diazepam and lidocaine was measured in patients with renal disease (those with uremia, nephrotic syndrome, or who had received a transplant) and in age- and sex-matched control subjects. Percentage unbound diazepami in plasma was increased over control in all three groups of patients as follows: uremic patients 3.23%, control, 1.64% (P < 0.001), nephrotic patients, 3.55%, control, 1.63% (P < 0.001); and transplant recipients, 2.11 %, control 1.50% (P < 0.001). The binding ratio (molar concentration of bound to unbound drug) in the patients was related to albumin concentration (r = 0.609, P < 0.001). Percentage of unbound lidocaine did not differ substantially from control in nephrotic patients (34.2%, control 30.8%a), but was reduced in the uremic patients (20.8%, control 30.7%, P < 0.001) and transplant recipients (24.6%, control 33.7%, P < 0.005). These increases were associated with increases in al-acid glycoprotein (AAG) concentration (uremic patients 134.9 mg/dl, control 66.3, P < 0.001; transplant recipients 106.5, control 65.6, P < 0.001). The binding ratio of lidocaine was closely related to the AAG concentration in patients (r = 0.933, P < 0.001) and controls (r = 0.719, P < 0.001). Thus, the binding of basic drugs may be increased or decreased in patients with renal disease, depending on the relative contribution of the individual plasma proteins to the total binding and the type of disease.

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