Assaying protein unbound drugs using microdialysis techniques

Tsai, Tung Hu

doi:10.1016/j.jchromb.2003.08.036

Cited by 115 publications

(75 citation statements)

References 122 publications

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“…Several steps for quality experiments including retention time, spiking of authentic standard, change of wavelength and change of the composition of mobile phase were used to examine the contents in EbM extracts. 13 To standardize and quantify the EbM extracts, icariin (C 33 H 40 O 15 , molecular weight: 676.65 Da) was used as an internal standard with a chromatograph column (Acq-Tac, Waters, Kyoto, Japan) and a UV detector (G1314A, Agilent, Waldbronn, Germany). 11,12 Furthermore, the L-arginine level was determined and quantified by HPLC analysis with a chromatograph column (38023-11, Cosmosil, Kyoto, Japan) as described previously.…”

Section: Liquid Chromatographymentioning

confidence: 99%

Epimedium brevicornum Maxim extract relaxes rabbit corpus cavernosum through multitargets on nitric oxide/cyclic guanosine monophosphate signaling pathway

Tm³

et al. 2006

Int J Impot Res

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Epimedium brevicornum Maxim (EbM) has been reputed to have sexual stimulation effects on males. The study is aimed to test the hypothesis that EbM extracts relaxed the corpus cavernosum (CC) smooth muscle through activation of multitargets on nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway. Water extract of EbM and its subfraction (EP-20) were prepared and standardized by high-performance liquid chromatography. Isolated rabbit CC strips were mounted in organ baths and isometric tension was recorded in the presence or absence of specific inhibitors related to NO/cGMP signaling such as L-N G -nitro-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ, a guanylyl cyclase inhibitor) or phosphodiesterase 5 (PDE 5) inhibitors. cGMP level was determined in EP-20-treated CC strips. The results showed that EP-20 enriched the content of L-arginine in the process of purification and relaxed the CC smooth muscle precontracted with phenylephrine (PE, 1 lM) in a concentrationdependent manner. Besides, EP-20 increased the amount of cGMP production in rabbit CC tissues. Coincubation with EP-20 and L-NAME or ODQ significantly decreased EP-20-induced relaxation whereas EP-20 increased sodium nitroprusside-induced relaxation in PE-precontracted CC strips. Besides, EP-20 increased the potency and the duration of the relaxation effects caused by electrical field stimulation. Finally, EP-20 could potentiate PDE 5 inhibitors in relaxation of PE-precontracted CC strips. We concluded that extract of EbM relax the CC smooth muscle through multitargets in NO/cGMP/PDE 5 pathway and might bring into perspective the treatment strategy for those patients with erectile dysfunction.

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Section: Liquid Chromatographymentioning

confidence: 99%

Epimedium brevicornum Maxim extract relaxes rabbit corpus cavernosum through multitargets on nitric oxide/cyclic guanosine monophosphate signaling pathway

Tm³

et al. 2006

Int J Impot Res

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“…Therefore, the question of whether interstitial glutamate, GABA, taurine, and glycine levels measured using microdialysis represent synaptic activity is quite controversial. [2][3][4][5] To clarify the origin of interstitial glutamate in the brain, Rooyackers has reviewed current studies on this issue. 114 Many fi ndings have suggested that extracellular glutamate mainly represents the neurotransmitter functions of glutamate, but confl icting conclusions have also been drawn.…”

Section: Amino Acidsmentioning

confidence: 99%

“…1 The method has been used extensively in animal and human studies for decades. [1][2][3][4][5] Pharmacodynamics (PD) is the study of the biochemical and physiological effects of drugs on the body. In a more quantitative sense, it describes the relationship between drug concentration and effect.…”

Section: Introductionmentioning

confidence: 99%

Microdialysis as a tool in local pharmacodynamics

Peris

Zhong

et al. 2006

AAPS J

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A BSTRACTIn many cases the clinical outcome of therapy needs to be determined by the drug concentration in the tissue compartment in which the pharmacological effect occurs rather than in the plasma. Microdialysis is an in vivo technique that allows direct measurement of unbound tissue concentrations and permits monitoring of the biochemical and physiological effects of drugs throughout the body. Microdialysis was fi rst used in pharmacodynamic research to study neurotransmission, and this remains its most common application in the fi eld. In this review, we give an overview of the principles, techniques, and applications of microdialysis in pharmacodynamic studies of local physiological events, including measurement of endogenous substances such as acetylcholine, catecholamines, serotonin, amino acids, peptides, glucose, lactate, glycerol, and hormones. Microdialysis coupled with systemic drug administration also permits the more intensive examination of the pharmacotherapeutic effect of drugs on extracellular levels of endogenous substances in peripheral compartments and blood. Selected examples of the physiological effects and mechanisms of action of drugs are also discussed, as are the advantages and limitations of this method. It is concluded that microdialysis is a reliable technique for the measurement of local events, which makes it an attractive tool for local pharmacodynamic research.

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“…Simultaneous monitoring of brain monoamine level changes by the in vivo microdialysis sampling technique is an important tool in the discovery of new drug therapies for a large number of neurologic disorders, such as Parkinson's disease, Alzheimer's disease, epilepsy, and neuropsychiatric disorders (Garrison et al, 2002). The advantages of the microdialysis technique include not only simultaneous sampling at multiple sites, such as the brain (Gottås et al, 2013), but also that there is no need for sample preparation because the dialysis membrane excludes proteins from the aqueous sample (Tsai, 2003). The use of ionpair high-performance liquid chromatography-electrochemical detection (HPLC-ECD) is of great interest for the determination of monoamine neurotransmitters [i.e., norepinephrine; epinephrine; 3,4-dihydroxyphenylacetic acid (DOPAC); DA; 5-hydroxyindole-3-acetic acid (5-HIAA); homovanillic acid (HVA); 5-HT; and 3-methoxytyramine hydrochloride] in microdialysis samples (Bicker et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

The Drug-Drug Effects of Rhein on the Pharmacokinetics and Pharmacodynamics of Clozapine in Rat Brain Extracellular Fluid by In Vivo Microdialysis

Hou

Lin

et al. 2015

J Pharmacol Exp Ther

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Clozapine, an atypical antipsychotic agent, is highly effective in treatment-resistant schizophrenia; however, its major side effect is constipation. Instead of laxatives, rhein is a pharmacologically active component found in Rheum palmatum L., a medicinal herbal remedy for constipation. The purpose of this study is to determine whether rhein impacts the pharmacokinetics (PK) and pharmacodynamics (PD) of clozapine in brain when used to relieve clozapine-induced constipation. Here, we have investigated not only the PK of clozapine in blood but also the effects of rhein on the PK of clozapine in blood and in brain extracellular fluid together with the PD effects on neurotransmitters in extracellular fluid. The concentrations of clozapine and norclozapine in biologic samples were measured by ultra-performance liquid chromatography-tandem mass spectrometry. The drug-drug effects of rhein on extracellular neurotransmitter efflux in the rat medial prefrontal cortex (mPFC) produced by clozapine were assayed by highperformance liquid chromatography-electrochemical detection. The results demonstrate that the clozapine PK was nonlinear. Pretreatment with rhein for 7 days increased the total blood concentration of clozapine, but significantly reduced the unbound clozapine concentrations in the mPFC by approximately 3-fold. Furthermore, 7 days of rhein pretreatment thoroughly abolished the efflux of dopamine and its metabolite (3,4-dihydroxyphenylacetic acid) and altered the profile of homovanillic acid, another metabolite of dopamine, in the mPFC. In conclusion, rhein was found to substantially decrease clozapine and norclozapine concentrations in the mPFC dialysate, and this is accompanied by lower concentrations in the neurotransmitters in the same biophase. These findings suggest that a detailed clinical study for drug-drug interactions is recommended.

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Assaying protein unbound drugs using microdialysis techniques

Cited by 115 publications

References 122 publications

Epimedium brevicornum Maxim extract relaxes rabbit corpus cavernosum through multitargets on nitric oxide/cyclic guanosine monophosphate signaling pathway

Epimedium brevicornum Maxim extract relaxes rabbit corpus cavernosum through multitargets on nitric oxide/cyclic guanosine monophosphate signaling pathway

Microdialysis as a tool in local pharmacodynamics

The Drug-Drug Effects of Rhein on the Pharmacokinetics and Pharmacodynamics of Clozapine in Rat Brain Extracellular Fluid by In Vivo Microdialysis

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