Effect of experimental renal dysfunction on bioavailability of ajmaline in rats

Hashimoto, Yoshiaki; Aiba, Tetsuya; Yasuhara, Masato; Hori, Ryohei

doi:10.1211/0022357011776153

Cited by 12 publications

(14 citation statements)

References 27 publications

(33 reference statements)

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“…5,[18][19][20] That is, we found that the intestinal absorption rate of propranolol and tacrolimus is significantly increased in rats with cisplatin-induced renal dysfunction. 5,18) We also reported that the intestinal absorption rate of ajmaline is significantly increased in rats with uranyl nitrate-induced renal failure.…”

Section: Discussionmentioning

confidence: 72%

“…7) We have investigated the effect of renal failure on the hepatic extraction of cationic drugs following intra-portal infusion. 5,19) The hepatic extraction of ajmaline in rats with uranyl nitrate-induced renal dysfunction was not significantly different from that in control rats. 19) Similarly, the hepatic extraction of propranolol was not altered significantly in rats with cisplatin-induced ARF.…”

Section: Discussionmentioning

confidence: 92%

“…21) The activity of CYP2D2, which is responsible for the metabolism of cationic drugs in the rat liver, may not be altered in renal failure. 5,7,19) That is, we previously reported that debrisoquine 4-hydroxylation activities in rat liver microsomes were not altered in rats with glycerol-, cisplatin-, nephrectomy-, and BUL-induced renal failure. 7) We have investigated the effect of renal failure on the hepatic extraction of cationic drugs following intra-portal infusion.…”

Section: Discussionmentioning

confidence: 93%

“…5,18) We also reported that the intestinal absorption rate of ajmaline is significantly increased in rats with uranyl nitrate-induced renal failure. 19) Moreover, Kimura et al 20) reported that the intestinal absorption rate of sulfanilic acid is increased in rats with HgCl 2 -induced renal dysfunction and in five-sixths nephrectomized rats. These findings suggested that the intestinal barrier function is decreased by reduced renal function, and that the absorption rate-dependent decrease in the hepatic first-pass clearance of propranolol due to saturation kinetics can be one of the most plausible mechanisms responsible for the increased bioavailability of propranolol in patients with renal failure.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics and Hepatic Extraction of Metoprolol in Rats with Glycerol-Induced Acute Renal Failure

Tanabe

Taira

Taguchi

et al. 2007

Biological & Pharmaceutical Bulletin

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The intestinal absorption of orally administered propranolol is essentially complete, with no metabolism of this drug occurring in the gut.1,2) After the oral administration of propranolol, the liver is the principal site of extensive presystemic and systemic metabolism, and less than 1% of the intact drug is found in urine.1,3) However, Bianchetti et al. 4) showed that the area under the concentration-time curve for orally administered propranolol in renal failure patients not on hemodialysis is 7-to 8-fold higher than that in healthy volunteers. We investigated the mechanisms responsible for the increased bioavailability of propranolol in rats with cisplatin-induced renal failure.5) The hepatic intrinsic clearance of propranolol was not significantly altered in rats with renal failure as compared with control rats. However, hepatic firstpass extraction of propranolol was dose-dependent and saturable in both renal failure and control rats, and the initial rate of absorption of the drug from the intestine was significantly greater in rats with renal failure than in control rats. Accordingly, the increased bioavailability of propranolol in rats with cisplatin-induced renal dysfunction is mainly a result of the increased initial absorption rate in the intestine followed by the partial saturation of hepatic first-pass metabolism. 5)Interestingly, the mechanism responsible for the increased bioavailability of propranolol in bilateral ureter-ligated (BUL) rats is different from that in rats with cisplatin-induced renal failure. 2,6) We investigated the pharmacokinetics of propranolol and metoprolol in BUL rats, and found that the rate of intestinal absorption of these drugs was only slightly greater than that in control rats.6) On the other hand, the arterial blood concentrations of propranolol and metoprolol following intra-portal infusion were significantly higher in BUL rats than control rats. 6) Therefore, the increased bioavailability of propranolol and metoprolol in BUL rats was attributed to diminished hepatic first-pass metabolism. The activity of CYP2D2, which is responsible for the metabolism of propranolol and metoprolol in the rat liver, was not altered by BUL, whereas the rate at which NADPH was generated in the liver cytosolic fraction was lower in BUL than control rats. [6][7][8] In addition, endogenous uremic substances are not involved in the reduced hepatic extraction of metoprolol in BUL rats. 9) Accordingly, the decrease in the hepatic metabolic activity and extraction of propranolol and metoprolol in BUL rats is mainly due to the reduced generation of NADPH in the liver.Since the sequence and relative importance of pathophysiological components of acute renal failure in patients are not clearly defined, it is difficult to determine which experimental method for producing renal failure in animals yields results that are most representative of the clinical condition. 10) We consider that the investigation of pharmacokinetics in other renal failure models is indispensable in order to understand the ...

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics and Hepatic Extraction of Metoprolol in Rats with Glycerol-Induced Acute Renal Failure

Tanabe

Taira

Taguchi

et al. 2007

Biological & Pharmaceutical Bulletin

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“…[53] This compound was named after Hakim Ajmal Khan, a Unani medical practitioner from South Asia. [54] It is found in Catharanthus roseus [55] and most species of Rauwolfia genus but its concentration is too low when extracted from the root part and also its bioavailability is lesser [56] hence, a semisynthetic propyl derivative called prajmaline was developed that had a better absorption and bioavailability as compared to Ajmaline. [57] …”

Section: Medicinally Active Chemical Constituents Of R Serpentinementioning

confidence: 99%

Untitled

Singh

2017

IJGP

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Rauwolfia serpentina is reported in an Ayurvedic medicinal system for centuries, for the treatment of various ailments such as snakebites, insomnia, hypertension, and insanity. Scientific evaluation of these documents can be valuable for finding new potential use in neurological disorders. The work presents the brief overview of R. serpentina including a description of the plant, its active chemical constituents and pharmacological properties with the major emphasis on cardiovascular and central nervous system disorders. This review compiles information available in the scientific literature from databases such as Science Direct, PubMed, India bioscience. org, Herbs -Medicinal plant usage and Identification Database, Database on medicinal plants used in Ayurveda and Siddha, Missouri Botanical Garden, National Medicinal Plants Board, and the International Plant Names Index. Information gathered from the literature has shown that the alkaloids are the major constituents of the plant imparting various pharmacological properties. Reserpine, the Indole alkaloid, is the most active compound of R. serpentine. The plant is known to possess antidiarrheal, antimicrobial activity apart from using it for the treatment of circulatory disorders, rheumatism, hypertension, insanity, epilepsy, and leaves are used in the removal of opacities of the cornea. Research shows that R. serpentine is a potential source of compounds pertaining medicinal applications. It provides an interesting subject in the search for new drugs of natural origin.

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Altered electrolyte handling of the choroid plexus in rats with glycerol‐induced acute renal failure

Ishikawa

Kono

Sakae

et al. 2010

Biopharm & Drug Disp

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The altered electrolyte handling of the choroid plexus was investigated in rats with acute renal failure (ARF) using lithium and rubidium as surrogate markers for sodium and potassium, respectively. Firstly, the transport of these two markers from the plasma to cerebrospinal fluid (CSF) was evaluated after they were concurrently injected into the femoral vein. As a result, their disposition from the plasma to CSF was shown to decrease in ARF rats, but the relationship profile between those two markers was not different from that observed in normal rats, indicating that the decreased disposition of lithium and rubidium occurs without affecting the stoichiometric balance. To clarify the mechanisms accounting for the decreased disposition, an inhibition study was then performed. When bumetanide, an inhibitor of the Na(+) /K(+) /2Cl(-) co-transporter, was directly introduced into the cerebroventricle prior to lithium and rubidium being intravenously administered, a marked increase in the markers' disposition was observed. However, such an increased disposition did not occur when bumetanide was injected into the femoral vein. Other inhibitors, such as amiloride for the Na(+) /H(+) exchanger and ouabain for Na(+) /K(+) -ATPase, did not show any effects on marker disposition regardless of the inhibitor being administered into either the cerebroventricle or femoral vein. These findings suggest that the decreased marker disposition in ARF rats is due to an increased efflux process of the choroid plexus mediated by the Na(+) /K(+) /2Cl(-) co-transporter. That is, electrolyte efflux from the CSF to plasma increases, and thereby the electrolyte influx from the plasma to CSF is counteracted.

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Effect of experimental renal dysfunction on bioavailability of ajmaline in rats

Cited by 12 publications

References 27 publications

Pharmacokinetics and Hepatic Extraction of Metoprolol in Rats with Glycerol-Induced Acute Renal Failure

Pharmacokinetics and Hepatic Extraction of Metoprolol in Rats with Glycerol-Induced Acute Renal Failure

Untitled

Altered electrolyte handling of the choroid plexus in rats with glycerol‐induced acute renal failure

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