The Effects of N‐Benzoyl‐β‐alanine, a New Nephroprotective Drug, on the Distribution and Renal Excretion of Enprofylline in Rats

LI WANG, TAKAAKI HASEGAWA, MASAYUKI NADAI, Toshitaka Nabeshima

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Abstract— The effects of the new nephroprotective drug N‐benzoyl‐β‐alanine (BA) on the disposition and renal excretion of the bronchodilator enprofylline, which is actively secreted in urine, were investigated in rats. Enprofylline was administered intravenously at a dosage of 2·5 mg kg−1 under three different steady‐state plasma BA concentrations (100,200 and 400 μg mL−1) which were achieved by constant infusion rates. Pharmacokinetic parameters for both total and unbound enprofylline were estimated by model‐independent methods. The presence of BA (400 μg mL−1) increased the systemic clearance by 25% and the volume of distribution at steady‐state by 90%. A significant increase in the dissociation constant, which is the protein binding parameter of enprofylline was observed in the presence of BA (400 μg mL−1), indicating that BA competitively inhibits the protein binding of enprofylline. However, BA significantly decreased the systemic clearance and volume of distribution for unbound enprofylline. These results suggest that BA, the organic anion transport inhibitor, inhibits renal excretion of enprofylline with a high affinity for renal tubular secretion, although the unbound concentration of enprofylline increases with administration of BA. We conclude that BA decreases the renal tubular secretion of enprofylline probably by reducing the affinity of the tubular transport system, and that these changes have marked effects on the pharmacokinetic behaviour of enprofylline. 1993 Royal Pharmaceutical Society of Great Britain

Original languageEnglish
Pages (from-to)622-626
Number of pages5
JournalJournal of Pharmacy and Pharmacology
Volume45
Issue number7
DOIs
Publication statusPublished - 01-01-1993
Externally publishedYes

Fingerprint

Pharmaceutical Preparations
Protein Binding
Pharmacokinetics
enprofylline
Renal Elimination
Kidney
Bronchodilator Agents
Anions
Urine

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

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title = "The Effects of N‐Benzoyl‐β‐alanine, a New Nephroprotective Drug, on the Distribution and Renal Excretion of Enprofylline in Rats",
abstract = "Abstract— The effects of the new nephroprotective drug N‐benzoyl‐β‐alanine (BA) on the disposition and renal excretion of the bronchodilator enprofylline, which is actively secreted in urine, were investigated in rats. Enprofylline was administered intravenously at a dosage of 2·5 mg kg−1 under three different steady‐state plasma BA concentrations (100,200 and 400 μg mL−1) which were achieved by constant infusion rates. Pharmacokinetic parameters for both total and unbound enprofylline were estimated by model‐independent methods. The presence of BA (400 μg mL−1) increased the systemic clearance by 25{\%} and the volume of distribution at steady‐state by 90{\%}. A significant increase in the dissociation constant, which is the protein binding parameter of enprofylline was observed in the presence of BA (400 μg mL−1), indicating that BA competitively inhibits the protein binding of enprofylline. However, BA significantly decreased the systemic clearance and volume of distribution for unbound enprofylline. These results suggest that BA, the organic anion transport inhibitor, inhibits renal excretion of enprofylline with a high affinity for renal tubular secretion, although the unbound concentration of enprofylline increases with administration of BA. We conclude that BA decreases the renal tubular secretion of enprofylline probably by reducing the affinity of the tubular transport system, and that these changes have marked effects on the pharmacokinetic behaviour of enprofylline. 1993 Royal Pharmaceutical Society of Great Britain",
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The Effects of N‐Benzoyl‐β‐alanine, a New Nephroprotective Drug, on the Distribution and Renal Excretion of Enprofylline in Rats. / WANG, LI; HASEGAWA, TAKAAKI; NADAI, MASAYUKI; Nabeshima, Toshitaka.

In: Journal of Pharmacy and Pharmacology, Vol. 45, No. 7, 01.01.1993, p. 622-626.

Research output: Contribution to journalArticle

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N2 - Abstract— The effects of the new nephroprotective drug N‐benzoyl‐β‐alanine (BA) on the disposition and renal excretion of the bronchodilator enprofylline, which is actively secreted in urine, were investigated in rats. Enprofylline was administered intravenously at a dosage of 2·5 mg kg−1 under three different steady‐state plasma BA concentrations (100,200 and 400 μg mL−1) which were achieved by constant infusion rates. Pharmacokinetic parameters for both total and unbound enprofylline were estimated by model‐independent methods. The presence of BA (400 μg mL−1) increased the systemic clearance by 25% and the volume of distribution at steady‐state by 90%. A significant increase in the dissociation constant, which is the protein binding parameter of enprofylline was observed in the presence of BA (400 μg mL−1), indicating that BA competitively inhibits the protein binding of enprofylline. However, BA significantly decreased the systemic clearance and volume of distribution for unbound enprofylline. These results suggest that BA, the organic anion transport inhibitor, inhibits renal excretion of enprofylline with a high affinity for renal tubular secretion, although the unbound concentration of enprofylline increases with administration of BA. We conclude that BA decreases the renal tubular secretion of enprofylline probably by reducing the affinity of the tubular transport system, and that these changes have marked effects on the pharmacokinetic behaviour of enprofylline. 1993 Royal Pharmaceutical Society of Great Britain

AB - Abstract— The effects of the new nephroprotective drug N‐benzoyl‐β‐alanine (BA) on the disposition and renal excretion of the bronchodilator enprofylline, which is actively secreted in urine, were investigated in rats. Enprofylline was administered intravenously at a dosage of 2·5 mg kg−1 under three different steady‐state plasma BA concentrations (100,200 and 400 μg mL−1) which were achieved by constant infusion rates. Pharmacokinetic parameters for both total and unbound enprofylline were estimated by model‐independent methods. The presence of BA (400 μg mL−1) increased the systemic clearance by 25% and the volume of distribution at steady‐state by 90%. A significant increase in the dissociation constant, which is the protein binding parameter of enprofylline was observed in the presence of BA (400 μg mL−1), indicating that BA competitively inhibits the protein binding of enprofylline. However, BA significantly decreased the systemic clearance and volume of distribution for unbound enprofylline. These results suggest that BA, the organic anion transport inhibitor, inhibits renal excretion of enprofylline with a high affinity for renal tubular secretion, although the unbound concentration of enprofylline increases with administration of BA. We conclude that BA decreases the renal tubular secretion of enprofylline probably by reducing the affinity of the tubular transport system, and that these changes have marked effects on the pharmacokinetic behaviour of enprofylline. 1993 Royal Pharmaceutical Society of Great Britain

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