Effects of salicylate on the pharmacokinetics of valproic acid after oral administration of sodium valproate in rats

Ohshiro, Susumu; Hobara, Norio; Sakai, Masayuki; Hokama, Nobuo; Kameya, Hiromasa; Sakanashi, Matao

doi:10.1163/15693910260698348

Cited by 4 publications

(5 citation statements)

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“…If this interaction was taking place in a patient whose epileptic seizures were wellcontrolled, the predicted concentration of VPA-Na would be lower than the therapeutic range and seizures may occur (Fudio et al 2006). As mentioned above, we have reported a similar effect of salicylate on the pharmacokinetics of VPA after oral administration of VPA-Na in rats (Ohshiro et al 2003). In this paper, salicylic acid was administered orally after oral VPA-Na; the plasmaVPA concentrations, including C max and AUC 0-3 , were significantly decreased compared with those in the control group.…”

Section: Resultssupporting

confidence: 64%

“…Sodium valproate (VPA-Na) is a branched-chain fatty acid that is used in the treatment of absence seizures, myoclonus and, usually in combination with other traditional anticonvulsants, in generalized epilepsy (Meunier et al 1963). We have reported the effect of salicylate on the pharmacokinetics of valproic acid (VPA) after oral administration of VPA-Na in rats (Ohshiro et al 2003). In that paper, the plasma VPA concentrations, including maximum plasma concentration (C max ) and area under the plasma concentrationtime curve up to 3 h (AUC 0-3 ), were significantly decreased compared with those in the control group, and these results suggest that they may be related to reduction of VPA absorption.…”

mentioning

confidence: 97%

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Investigation of low levels of plasma valproic acid concentration following simultaneous administration of sodium valproate and rizatriptan benzoate

Hokama

Hobara

Kameya

et al. 2007

Journal of Pharmacy and Pharmacology

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Drug interaction between rizatriptan benzoate, an anti-migraine agent, and sodium valproate (VPA-Na), an anticonvulsant, was studied in rats. When rizatriptan benzoate was administered orally immediately after VPA-Na oral administration, the pharmacokinetic parameters, such as plasma valproic acid (VPA) and area under the plasma concentration-time curve up to 3 h (AUC(0-3)), were significantly decreased compared with those in the control group. However, when rizatriptan benzoate was administered intraperitoneally immediately after VPA-Na orally, these parameters were not changed. In addition, when benzoic acid was administered orally immediately after VPA-Na orally, these were significantly lower compared with the control values. Therefore, it might be possible that VPA transport by monocarboxylate transporter was competitively inhibited by rizatriptan benzoate and thus absorption of VPA was decreased.

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Section: Resultssupporting

confidence: 64%

mentioning

confidence: 97%

Investigation of low levels of plasma valproic acid concentration following simultaneous administration of sodium valproate and rizatriptan benzoate

Hokama

Hobara

Kameya

et al. 2007

Journal of Pharmacy and Pharmacology

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“…In this study conditions, accumulation of lipid following 14 days exposure was not observed. Given the fact that the selected dose range (25-100 lM) was much lower than acute 24-h studies (1-3 mM) (Lee et al, 2008) and C max values found in rat plasma (Blotnik et al, 1996;Ohshiro et al, 2003), it may be speculated that higher concentrations might have been necessary to elicit a steatogenic response. Further incubation of rat hepatocytes with higher concentration of VPA (500-3000 lM) for 72 h resulted into dose-dependent accumulation of neutral lipids (Suppl.…”

Section: Discussionmentioning

confidence: 95%

“…(0.6-2.14) (Fruncillo et al, 1985;Rodrigues et al, 2012) Phospholipidosis (Halliwell, 1997) (2.32-3.72) # Phospholipidosis (Poucell et al, 1984) Neutral Lipids " Phospholipids " (1.33-33.52) (Lakshmi and Rajesh, 2011;Varanasi et al, 2008) Mitochondrial impairment (Feinstein et al, 2005) (1.35-2) # Hepatocellular damage (Floyd et al, 2009) (Imamura et al, 1988;Zhang et al, 2007) Cholestasis ( Barth et al, 1978), Hyperbilirubinemia (Obata, 1983), Phospholipidosis (Hirode et al, 2008) (0.07-0.42) # Cholestasis (Regal et al, 1987), Hyperbilirubinemia (Waitzkin, 1962), Phospholipidosis (Halliwell, 1997 (566.82-1292.86) (Blotnik et al, 1996;Ohshiro et al, 2003) Mitochondrial impairment (Tong et al, 2005), Steatosis (Lewis et al, 1982) ( of scanned images confirmed that the average intensity and the average area of fluorescent signal were significantly higher in hepatocytes cultured with 4 layers of Matrigel™ ( Fig. 2D and E).…”

Section: Improved Cellular Morphology and Functionality By Addition Omentioning

confidence: 99%

Determination of liver specific toxicities in rat hepatocytes by high content imaging during 2-week multiple treatment

Germano

Uteng

Philippe

et al. 2015

Toxicology in Vitro

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DILI is a major safety issue during drug development and one of the leading causes for market withdrawal. Despite many efforts made in the past, the prediction of DILI using in vitro models remains very unreliable. In the present study, the well-established hepatocyte Collagen I-Matrigel™ sandwich culture was used, mimicking chronic drug treatment after multiple incubations for 14 days. Ten drugs associated with different types of specific preclinical and clinical liver injury were evaluated at non-cytotoxic concentrations. Mrp2-mediated transport, intracellular accumulation of neutral lipids and phospholipids were selected as functional endpoints by using Cellomics™ Arrayscan® technology and assessed at five timepoints (day 1, 3, 7, 10, 14). Liver specific functional impairments after drug treatment were enhanced over time and could be monitored by HCI already after few days and before cytotoxicity. Phospholipidosis-inducing drugs Chlorpromazine and Amiodarone displayed the same response as in vivo. Cyclosporin A, Chlorpromazine, and Troglitazone inhibited Mrp2-mediated biliary transport, correlating with in vivo findings. Steatosis remained difficult to be reproduced under the current in vitro testing conditions, resulting into false negative and positive responses. The present results suggest that the repeated long-term treatment of rat hepatocytes in the Collagen I-Matrigel™ sandwich configuration might be a suitable tool for safety profiling of the potential to induce phospholipidosis and impair Mrp2-mediated transport processes, but not to predict steatosis.

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“…An unexpected change in valproic acid (VPA) concentration after VPA-Na administration might be caused by some co-administered drugs (9,16). In addition, we reported that salicylate (15) and rizatriptan benzoate (8) affected plasma VPA concentration in rats. Therefore, many clinical situations may need reliable therapeutic drug monitoring of VPA for the appropriate dose because of unpredictable drug-interactions.…”

mentioning

confidence: 98%

Effects of a dopamine receptor agonist and atropine sulfate on absorption of valproic acid in rats

Kameya¹,

Hokama²,

Hobara³

et al. 2009

Biomed. Res.

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The aim of this study is to determine whether pramipexole hydrochloride hydrate (PHH) and atropine sulfate affect valproic acid (VPA) pharmacokinetics and to evaluate how plasma VPA concentrations are altered by different PHH administration routes. The following studies were conducted on rats: 1) changes in plasma VPA concentration after simultaneous oral administration (PO) of PHH and VPA-Na; 2) effects of intraperitoneal administration (IP) of PHH on plasma VPA concentration after VPA-Na PO; 3) effects of PHH PO on plasma VPA concentration after intravenous administration (IV) of VPA-Na; and 4) changes in plasma VPA concentration after simultaneous PO of atropine sulfate and VPA-Na. Atropine sulfate PO significantly decreased the area under the concentration-time curve up to 3 h (AUC0-3, the total amount of drug plasma concentration) of VPA, suggesting that atropine sulfate decreases VPA-Na absorption probably due to reduced gastrointestinal motility by its anticholinergic action. Similarly, by PHH PO or IP, VPA AUC0-3 was significantly decreased. However, in cases of VPA-Na IV, all VPA parameters were unchanged by PHH PO. These results indicate that the PHH inhibitory effect may be caused in the absorption phase of VPA by pharmacological action of PHH, and thus PHH decreases VPA-Na bioavailability.Sodium valproate (VPA-Na, monosodium 2-propylpentanoate) is a straight-chain alkyl monocarboxylic acid with the chemical formula C 8 H 16 O 2 . VPA-Na possesses a broad antiepileptic spectrum, and is used as a first-line treatment for patients with generalized and partial seizures (1, 11). It is strongly suggested that the pharmacological effects of VPA may increase the concentration of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter to brain neurons, or enhance the action of GABA at postsynaptic receptor sites (7). An unexpected change in valproic acid (VPA) concentration after VPA-Na administration might be caused by some co-administered drugs (9, 16). In addition, we reported that salicylate (15) and rizatriptan benzoate (8) affected plasma VPA concentration in rats. Therefore, many clinical situations may need reliable therapeutic drug monitoring of VPA for the appropriate dose because of unpredictable drug-interactions. Pramipexole hydrochloride hydrate (PHH, S-2-Amino-4,5,6,7-tetrahydro-6-propylaminobenzothiazole dihydrochloride hydrate), a direct-acting dopamine receptor agonist, is effective in treatment of Parkinson's disease, and selectively binds to dopamine D2 and D3 receptors with high affinity (13,17,22). VPA-Na is often prescribed in combination with PHH. It is known that dopamine agonists can depress gastrointestinal motility. Thus, in patients given PHH, it is considered that gastrointestinal motility declines due to the D2 receptor agonistic activity of PHH, subsequently affecting VPA pharmacokinetics. However, until now, there is no report addressing VPA-PHH interactions. Therefore, we investigated whether PHH and atropine sulfate, a tion after intravenous administration (IV...

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Effects of salicylate on the pharmacokinetics of valproic acid after oral administration of sodium valproate in rats

Cited by 4 publications

References 1 publication

Investigation of low levels of plasma valproic acid concentration following simultaneous administration of sodium valproate and rizatriptan benzoate

Investigation of low levels of plasma valproic acid concentration following simultaneous administration of sodium valproate and rizatriptan benzoate

Determination of liver specific toxicities in rat hepatocytes by high content imaging during 2-week multiple treatment

Effects of a dopamine receptor agonist and atropine sulfate on absorption of valproic acid in rats

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