Protein Binding of Indomethacin: Binding of Indomethacin to Human Plasma Albumin and its Displacement from Binding by Ibuprofen, Phenylbutazone and Salicylate, &lt;i&gt;in vitro&lt;/i&gt;

Mason, R.W.; McQueen, E. G.

doi:10.1159/000136516

Cited by 68 publications

(24 citation statements)

References 14 publications

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“…Using the published pharmacokinetic parameters of indomethacin in rats (Ogiso et al, 1989), the starting plasma concentration (C 0 ) of indomethacin at the dose given in this study is predicted to be 83.3 g/ml. Given that indomethacin is about 90% bound in plasma (Mason and McQueen, 1974), the free concentration of indomethacin would be 8.3 g/ml. It has also been shown that indomethacin can interact with MRP4 at a concentration low as 0.375 g/ml (1 M) (Reid et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Distribution of the Novel Antifolate Pemetrexed to the Brain

Dai¹,

Chen

Elmquist

2005

J Pharmacol Exp Ther

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Pemetrexed disodium is a novel antifolate that exhibits potent inhibitory effects on multiple enzymes in folate metabolism. Phase II/III clinical trials have shown that pemetrexed is effective against various solid tumors. Like methotrexate, pemetrexed may be useful in treatment of primary and secondary brain tumors. In this study, we examined the central nervous system (CNS) distribution of pemetrexed and the interaction with an organic anion transport inhibitor indomethacin. Male Wistar rats were administered pemetrexed by either single intravenous bolus or constant intravenous infusion. Unbound pemetrexed in blood and brain was measured by simultaneous arterial blood and frontal cortex microdialysis sampling. In the i.v. bolus experiments, indomethacin was administered by i.v. bolus (10 mg/kg) followed by i.v. infusion (0.1 mg/kg/h) in a crossover manner. In the infusion experiments, the same dose of indomethacin was administered after a steady state was reached for pemetrexed. CNS distributional kinetics was analyzed by compartmental and noncompartmental methods. Both bolus and infusion studies showed that pemetrexed has a limited CNS distribution. The mean area under concentrationtime curve (AUC) brain /AUC plasma ratio of unbound pemetrexed was 0.078 Ϯ 0.038 in the i.v. bolus study. The pemetrexed steady-state brain-to-plasma unbound concentration ratio after i.v. infusion was 0.106 Ϯ 0.054. The distributional clearance into the brain was approximately 10% of the clearance out of the brain in both the compartmental and noncompartmental analyses. Indomethacin had no effect on either the brain-toplasma AUC ratio or the steady-state brain-to-plasma concentration ratio. The distribution of pemetrexed into the brain is limited, and an efflux clearance process, such as an efflux transporter, may be involved.

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Section: Discussionmentioning

confidence: 99%

Distribution of the Novel Antifolate Pemetrexed to the Brain

Dai¹,

Chen

Elmquist

2005

J Pharmacol Exp Ther

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“…Mason and McQueen [ 13] have measured indomethacin binding to pooled adult human plasma with a known content of albumin. Our binding isotherm is consistent with the one reported by these authors confirming the validity of the experimental observations.…”

Section: Discussionmentioning

confidence: 99%

Interaction of Indomethacin with Adult Human Albumin and Neonatal Serum

Honoré¹,

Brodersen²,

Robertson³

1983

Dev Pharmacol Ther

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The binding of indomethacin to albumin was investigated at 37 °C, pH 7.4. The first stoichiometric binding constant is 2.5 X 10^5 M^-1. Indomethacin utilizes both the bilirubin and diazepam binding functions equally. The effect on bilirubin binding to albumin is negligible at therapeutic indomethacin blood levels. Oleic acid does not affect indomethacin binding until the oleate/albumin molar ratio exceeds 2. A method for measuring the reserve albumin equivalent for binding indomethacin is described. Measurement of this reserve binding equivalent in 33 neonatal serum samples shows no significant correlation of the reserve binding to the albumin level. This methodology may be useful in studying the variable response of infants with patent ductus arteriosus to indomethacin.

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“…It is not necessarily valid to translate directly the results of experiments done in vitro to the situation in vivo. Nevertheless, it is worth mentioning that concentrations of indomethacin were much in excess of those needed (0.1 jg/ml) to inhibit ACTH-induced prostaglandin release in vitro from adrenal cortical cells of the cat (Laychock & Rubin, 1976), even accounting for protein binding of indomethacin (-90% in man; Mason & McQueen, 1974).…”

Section: Discussionmentioning

confidence: 99%

The Failure of Indomethacin to Alter Acth‐induced Adrenal Hyperaemia or Steroidogenesis in the Anaesthetized Dog

Gerber

Nies

1979

British J Pharmacology

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The response of adrenal blood flow to adrenocorticotropic hormone (ACTH) was measured with radioactive microspheres in anaesthetized, dexamethasone‐treated, mongrel dogs. Adrenocorticotropic hormone (2 u/h i.v.) increased adrenal blood flow within 15 min and this persisted for the duration of the infusion. Cortisol concentrations also rose with ACTH infusion. Indomethacin (6 mg/kg i.v. followed by 1 mg/min) did not affect the adrenal response to ACTH although plasma concentrations of indomethacin (21.9 ± 2.5 μg/ml) adequate to suppress prostaglandin synthesis were achieved. We conclude that prostaglandins are not required for steroidogenesis or the adrenal haemodynamic response to ACTH.

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Protein Binding of Indomethacin: Binding of Indomethacin to Human Plasma Albumin and its Displacement from Binding by Ibuprofen, Phenylbutazone and Salicylate, <i>in vitro</i>

Cited by 68 publications

References 14 publications

Distribution of the Novel Antifolate Pemetrexed to the Brain

Distribution of the Novel Antifolate Pemetrexed to the Brain

Interaction of Indomethacin with Adult Human Albumin and Neonatal Serum

The Failure of Indomethacin to Alter Acth‐induced Adrenal Hyperaemia or Steroidogenesis in the Anaesthetized Dog

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