Time-Dependent Changes in the Pharmacokinetics and Renal Excretion of Xanthine Derivative Enprofylline Induced by Bacterial Endotoxin in Rats

Masayuki Nadai, Takaaki Hasegawa, Li Wang, Soheila Haghgoo, Toshitaka Nabeshima, Nobuo Kato

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Time-dependent changes in the pharmacokinetics and renal handling of enprofylline induced by bacterial endotoxin (Klebsiella pneumoniae LPS) were investigated in rats. To evaluate the early effect of LPS on kidney functions and the renal excretion of enprofylline, which is an organic anion drug excreted primarily by an active tubular secretion, LPS (250μg/kg) was infused for 5 min under constant infusion at rates of 2.3 and 23 μg/min/kg for inulin and enprofylline, respectively. LPS caused a drop in the glomerular filtration rate (GFR), estimated as the renal clearance of inulin, to 65-75% of that observed in the control rats within 30 min after the LPS treatment. The renal clearance (CL r ) of enprofylline decreased in conjunction with GFR, while the percentage of decrease in the CL r was slightly greater than that in GFR. LPS-induced decreases in the CL r for enprofylline and GFR continued over the testing period of 120min. The time-dependent effect of LPS on the pharmacokinetics of enprofylline was examined by a single injection of enprofylline (2.5 mg/kg) to rats pretreated 2, 10 or 24h earlier with or without LPS. The pharmacokinetic parameters of enprofylline were determined by a model-independent method. Significant changes in the systemic clearance for enprofylline were observed in rats pretreated 2 and 10h earlier with LPS. but no such changes were observed in rats pretreated 24h earlier with LPS. These findings indicate the existence of a time-dependent effect of LPS on the pharmacokinetics of enprofylline, and suggest that LPS at a dose of 250 μg/kg, at least, does not induce cytotoxicity to kidney cells.

Original languageEnglish
Pages (from-to)1089-1093
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Volume18
Issue number8
DOIs
Publication statusPublished - 01-01-1995
Externally publishedYes

Fingerprint

Xanthine
Endotoxins
Pharmacokinetics
Glomerular Filtration Rate
Kidney
Inulin
enprofylline
Renal Elimination
Klebsiella pneumoniae
Anions
Injections

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

@article{d4d2a6659df84220bb875a1f4eb7115a,
title = "Time-Dependent Changes in the Pharmacokinetics and Renal Excretion of Xanthine Derivative Enprofylline Induced by Bacterial Endotoxin in Rats",
abstract = "Time-dependent changes in the pharmacokinetics and renal handling of enprofylline induced by bacterial endotoxin (Klebsiella pneumoniae LPS) were investigated in rats. To evaluate the early effect of LPS on kidney functions and the renal excretion of enprofylline, which is an organic anion drug excreted primarily by an active tubular secretion, LPS (250μg/kg) was infused for 5 min under constant infusion at rates of 2.3 and 23 μg/min/kg for inulin and enprofylline, respectively. LPS caused a drop in the glomerular filtration rate (GFR), estimated as the renal clearance of inulin, to 65-75{\%} of that observed in the control rats within 30 min after the LPS treatment. The renal clearance (CL r ) of enprofylline decreased in conjunction with GFR, while the percentage of decrease in the CL r was slightly greater than that in GFR. LPS-induced decreases in the CL r for enprofylline and GFR continued over the testing period of 120min. The time-dependent effect of LPS on the pharmacokinetics of enprofylline was examined by a single injection of enprofylline (2.5 mg/kg) to rats pretreated 2, 10 or 24h earlier with or without LPS. The pharmacokinetic parameters of enprofylline were determined by a model-independent method. Significant changes in the systemic clearance for enprofylline were observed in rats pretreated 2 and 10h earlier with LPS. but no such changes were observed in rats pretreated 24h earlier with LPS. These findings indicate the existence of a time-dependent effect of LPS on the pharmacokinetics of enprofylline, and suggest that LPS at a dose of 250 μg/kg, at least, does not induce cytotoxicity to kidney cells.",
author = "Masayuki Nadai and Takaaki Hasegawa and Li Wang and Soheila Haghgoo and Toshitaka Nabeshima and Nobuo Kato",
year = "1995",
month = "1",
day = "1",
doi = "10.1248/bpb.18.1089",
language = "English",
volume = "18",
pages = "1089--1093",
journal = "Biological and Pharmaceutical Bulletin",
issn = "0918-6158",
publisher = "Pharmaceutical Society of Japan",
number = "8",

}

Time-Dependent Changes in the Pharmacokinetics and Renal Excretion of Xanthine Derivative Enprofylline Induced by Bacterial Endotoxin in Rats. / Nadai, Masayuki; Hasegawa, Takaaki; Wang, Li; Haghgoo, Soheila; Nabeshima, Toshitaka; Kato, Nobuo.

In: Biological and Pharmaceutical Bulletin, Vol. 18, No. 8, 01.01.1995, p. 1089-1093.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Time-Dependent Changes in the Pharmacokinetics and Renal Excretion of Xanthine Derivative Enprofylline Induced by Bacterial Endotoxin in Rats

AU - Nadai, Masayuki

AU - Hasegawa, Takaaki

AU - Wang, Li

AU - Haghgoo, Soheila

AU - Nabeshima, Toshitaka

AU - Kato, Nobuo

PY - 1995/1/1

Y1 - 1995/1/1

N2 - Time-dependent changes in the pharmacokinetics and renal handling of enprofylline induced by bacterial endotoxin (Klebsiella pneumoniae LPS) were investigated in rats. To evaluate the early effect of LPS on kidney functions and the renal excretion of enprofylline, which is an organic anion drug excreted primarily by an active tubular secretion, LPS (250μg/kg) was infused for 5 min under constant infusion at rates of 2.3 and 23 μg/min/kg for inulin and enprofylline, respectively. LPS caused a drop in the glomerular filtration rate (GFR), estimated as the renal clearance of inulin, to 65-75% of that observed in the control rats within 30 min after the LPS treatment. The renal clearance (CL r ) of enprofylline decreased in conjunction with GFR, while the percentage of decrease in the CL r was slightly greater than that in GFR. LPS-induced decreases in the CL r for enprofylline and GFR continued over the testing period of 120min. The time-dependent effect of LPS on the pharmacokinetics of enprofylline was examined by a single injection of enprofylline (2.5 mg/kg) to rats pretreated 2, 10 or 24h earlier with or without LPS. The pharmacokinetic parameters of enprofylline were determined by a model-independent method. Significant changes in the systemic clearance for enprofylline were observed in rats pretreated 2 and 10h earlier with LPS. but no such changes were observed in rats pretreated 24h earlier with LPS. These findings indicate the existence of a time-dependent effect of LPS on the pharmacokinetics of enprofylline, and suggest that LPS at a dose of 250 μg/kg, at least, does not induce cytotoxicity to kidney cells.

AB - Time-dependent changes in the pharmacokinetics and renal handling of enprofylline induced by bacterial endotoxin (Klebsiella pneumoniae LPS) were investigated in rats. To evaluate the early effect of LPS on kidney functions and the renal excretion of enprofylline, which is an organic anion drug excreted primarily by an active tubular secretion, LPS (250μg/kg) was infused for 5 min under constant infusion at rates of 2.3 and 23 μg/min/kg for inulin and enprofylline, respectively. LPS caused a drop in the glomerular filtration rate (GFR), estimated as the renal clearance of inulin, to 65-75% of that observed in the control rats within 30 min after the LPS treatment. The renal clearance (CL r ) of enprofylline decreased in conjunction with GFR, while the percentage of decrease in the CL r was slightly greater than that in GFR. LPS-induced decreases in the CL r for enprofylline and GFR continued over the testing period of 120min. The time-dependent effect of LPS on the pharmacokinetics of enprofylline was examined by a single injection of enprofylline (2.5 mg/kg) to rats pretreated 2, 10 or 24h earlier with or without LPS. The pharmacokinetic parameters of enprofylline were determined by a model-independent method. Significant changes in the systemic clearance for enprofylline were observed in rats pretreated 2 and 10h earlier with LPS. but no such changes were observed in rats pretreated 24h earlier with LPS. These findings indicate the existence of a time-dependent effect of LPS on the pharmacokinetics of enprofylline, and suggest that LPS at a dose of 250 μg/kg, at least, does not induce cytotoxicity to kidney cells.

UR - http://www.scopus.com/inward/record.url?scp=0029146584&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029146584&partnerID=8YFLogxK

U2 - 10.1248/bpb.18.1089

DO - 10.1248/bpb.18.1089

M3 - Article

VL - 18

SP - 1089

EP - 1093

JO - Biological and Pharmaceutical Bulletin

JF - Biological and Pharmaceutical Bulletin

SN - 0918-6158

IS - 8

ER -