Effect of experimental renal dysfunction on bioavailability of ajmaline in rats

Y. Hashimoto, Tetsuya Aiba, M. Yasuhara, R. Hori

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The effect of renal dysfunction on the bioavailability of ajmaline has been investigated in rats, where experimental renal dysfunction was induced by subcutaneous injection of uranyl nitrate (10 mg kg-1). Renal dysfunction did not cause any change in the blood ajmaline concentration after intravenous administration (2 mg kg-1), but it increased the blood ajmaline concentration by approximately 2.8-fold after intraduodenal administration (10 mg kg-1). The availability of ajmaline in control rats was 16.7%, whereas the availability was increased to 41.1% in rats with renal dysfunction. The unbound fraction in the blood and the metabolic activity in the liver, was assessed with the 10 000-g supernatant fraction and with isolated hepatocytes, respectively. The values were found to be similar in both groups. The blood concentration following intraportal infusion was only slightly increased in rats with renal dysfunction, but the hepatic first-pass extraction was infusion rate-dependent and saturable. The initial absorption rate of ajmaline from the small intestine in rats with renal dysfunction was significantly greater compared with control rats. These results indicated that the increased availability of ajmaline in renal dysfunction was mainly a result of partially saturated extraction in the liver, which was caused by an increased absorption rate in the intestine and non-linear extraction in the liver.

Original languageEnglish
Pages (from-to)805-813
Number of pages9
JournalJournal of Pharmacy and Pharmacology
Volume53
Issue number6
DOIs
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Ajmaline
Biological Availability
Kidney
Liver
Uranyl Nitrate
Subcutaneous Injections
Intravenous Administration
Small Intestine
Intestines
Hepatocytes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Effect of experimental renal dysfunction on bioavailability of ajmaline in rats. / Hashimoto, Y.; Aiba, Tetsuya; Yasuhara, M.; Hori, R.

In: Journal of Pharmacy and Pharmacology, Vol. 53, No. 6, 2001, p. 805-813.

Research output: Contribution to journalArticle

@article{174778a1f30b4fe7ae40ab61588dcc70,
title = "Effect of experimental renal dysfunction on bioavailability of ajmaline in rats",
abstract = "The effect of renal dysfunction on the bioavailability of ajmaline has been investigated in rats, where experimental renal dysfunction was induced by subcutaneous injection of uranyl nitrate (10 mg kg-1). Renal dysfunction did not cause any change in the blood ajmaline concentration after intravenous administration (2 mg kg-1), but it increased the blood ajmaline concentration by approximately 2.8-fold after intraduodenal administration (10 mg kg-1). The availability of ajmaline in control rats was 16.7{\%}, whereas the availability was increased to 41.1{\%} in rats with renal dysfunction. The unbound fraction in the blood and the metabolic activity in the liver, was assessed with the 10 000-g supernatant fraction and with isolated hepatocytes, respectively. The values were found to be similar in both groups. The blood concentration following intraportal infusion was only slightly increased in rats with renal dysfunction, but the hepatic first-pass extraction was infusion rate-dependent and saturable. The initial absorption rate of ajmaline from the small intestine in rats with renal dysfunction was significantly greater compared with control rats. These results indicated that the increased availability of ajmaline in renal dysfunction was mainly a result of partially saturated extraction in the liver, which was caused by an increased absorption rate in the intestine and non-linear extraction in the liver.",
author = "Y. Hashimoto and Tetsuya Aiba and M. Yasuhara and R. Hori",
year = "2001",
doi = "10.1211/0022357011776153",
language = "English",
volume = "53",
pages = "805--813",
journal = "Journal of Pharmacy and Pharmacology",
issn = "0022-3573",
publisher = "Pharmaceutical Press",
number = "6",

}

TY - JOUR

T1 - Effect of experimental renal dysfunction on bioavailability of ajmaline in rats

AU - Hashimoto, Y.

AU - Aiba, Tetsuya

AU - Yasuhara, M.

AU - Hori, R.

PY - 2001

Y1 - 2001

N2 - The effect of renal dysfunction on the bioavailability of ajmaline has been investigated in rats, where experimental renal dysfunction was induced by subcutaneous injection of uranyl nitrate (10 mg kg-1). Renal dysfunction did not cause any change in the blood ajmaline concentration after intravenous administration (2 mg kg-1), but it increased the blood ajmaline concentration by approximately 2.8-fold after intraduodenal administration (10 mg kg-1). The availability of ajmaline in control rats was 16.7%, whereas the availability was increased to 41.1% in rats with renal dysfunction. The unbound fraction in the blood and the metabolic activity in the liver, was assessed with the 10 000-g supernatant fraction and with isolated hepatocytes, respectively. The values were found to be similar in both groups. The blood concentration following intraportal infusion was only slightly increased in rats with renal dysfunction, but the hepatic first-pass extraction was infusion rate-dependent and saturable. The initial absorption rate of ajmaline from the small intestine in rats with renal dysfunction was significantly greater compared with control rats. These results indicated that the increased availability of ajmaline in renal dysfunction was mainly a result of partially saturated extraction in the liver, which was caused by an increased absorption rate in the intestine and non-linear extraction in the liver.

AB - The effect of renal dysfunction on the bioavailability of ajmaline has been investigated in rats, where experimental renal dysfunction was induced by subcutaneous injection of uranyl nitrate (10 mg kg-1). Renal dysfunction did not cause any change in the blood ajmaline concentration after intravenous administration (2 mg kg-1), but it increased the blood ajmaline concentration by approximately 2.8-fold after intraduodenal administration (10 mg kg-1). The availability of ajmaline in control rats was 16.7%, whereas the availability was increased to 41.1% in rats with renal dysfunction. The unbound fraction in the blood and the metabolic activity in the liver, was assessed with the 10 000-g supernatant fraction and with isolated hepatocytes, respectively. The values were found to be similar in both groups. The blood concentration following intraportal infusion was only slightly increased in rats with renal dysfunction, but the hepatic first-pass extraction was infusion rate-dependent and saturable. The initial absorption rate of ajmaline from the small intestine in rats with renal dysfunction was significantly greater compared with control rats. These results indicated that the increased availability of ajmaline in renal dysfunction was mainly a result of partially saturated extraction in the liver, which was caused by an increased absorption rate in the intestine and non-linear extraction in the liver.

UR - http://www.scopus.com/inward/record.url?scp=0034986976&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034986976&partnerID=8YFLogxK

U2 - 10.1211/0022357011776153

DO - 10.1211/0022357011776153

M3 - Article

VL - 53

SP - 805

EP - 813

JO - Journal of Pharmacy and Pharmacology

JF - Journal of Pharmacy and Pharmacology

SN - 0022-3573

IS - 6

ER -