Concurrent monitoring of central carbamazepine and transmitter amine metabolism and motor activity in individual unrestrained rats using repetitive withdrawal of cerebrospinal fluid

Sokomba, Elijah; Patsalos, Philip N.; Lolin, Y. I.; Curzon, G.

doi:10.1016/0028-3908(88)90150-5

Cited by 22 publications

(15 citation statements)

References 17 publications

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“…In such an event, CSF may accurately reflect free plasma concentrations while providing an overestimation of drug concentrations in the extracellular fluid of the brain. Consistent with the blood-brain barrier impairment implied by these data, increases in the brain extracellular fluid levels of both carbamazepine and phenytoin have been reported in the presence of the MRP inhibitor probenecid and/or in MRP2-deficient TR Ϫ rats (Potschka et al, , 2003Loscher and Potschka, 2002) despite equivalent free plasma and CSF concentrations of these drugs in rats (Chou and Levy, 1981;Sokomba et al, 1988). In both cases, the observed impairment attributed to MRP2 efflux at the blood-brain barrier was enough to account for the differences between the unbound fractions and in vivo exposures reported in this analysis.…”

Section: Maurer Et Alsupporting

confidence: 65%

Relationship Between Exposure and Nonspecific Binding of Thirty-Three Central Nervous System Drugs in Mice

Maurer

DeBartolo²,

Tess³

et al. 2004

Drug Metab Dispos

207

171

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ABSTRACT:Unbound fractions in mouse brain and plasma were determined for 31 structurally diverse central nervous system (CNS) drugs and two active metabolites. Three comparisons were made between in vitro binding and in vivo exposure data, namely: 1) mouse brainto-plasma exposure versus unbound plasma-to-unbound brain fraction ratio (fu plasma /fu brain ), 2) cerebrospinal fluid-to-brain exposure versus unbound brain fraction (fu brain ), and 3) cerebrospinal fluid-to-plasma exposure versus unbound plasma fraction (fu plasma ). Unbound fraction data were within 3-fold of in vivo exposure ratios for the majority of the drugs examined (i.e., 22 of 33), indicating a predominately free equilibrium across the blood-brain and blood-CSF barriers. Some degree of distributional impairment at either the blood-CSF or the blood-brain barrier was indicated for 8 of the 11 remaining drugs (i.e., carbamazepine, midazolam, phenytoin, sulpiride, thiopental, risperidone, 9-hydroxyrisperidone, and zolpidem). In several cases, the indicated distributional impairment is consistent with other independent literature reports for these drugs. Through the use of this approach, it appears that most CNS-active agents freely equilibrate across the blood-brain and blood-CSF barriers such that unbound drug concentrations in brain approximate those in the plasma. However, these results also support the intuitive concept that distributional impairment does not necessarily preclude CNS activity.

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Section: Maurer Et Alsupporting

confidence: 65%

Relationship Between Exposure and Nonspecific Binding of Thirty-Three Central Nervous System Drugs in Mice

Maurer

DeBartolo²,

Tess³

et al. 2004

Drug Metab Dispos

207

171

View full text Add to dashboard Cite

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“…However, with the advent of more sensitive assay techniques such as enzyme-linked immunosorbent assay and high-performance liquid chromatography (Klockowski and Levy, 1987), the low CSF yield from rats is no longer a limitation in utilization for biomarker measurement in a variety of toxicities and neurological disorders. Numerous techniques have been described for CSF collection in rats permanently implanted with cannulae or by guided cannulae (Curzon et al, 1985;De La Riva and Yeo, 1985;Jolkkonen et al, 1986;Sanvitto et al, 1987;Dingemanse et al, 1988;Sokomba et al, 1988;Takemoto, 1991;Westergren and Johansson, 1991;Halonen et al, 1992;Consiglio and Lucion, 2000). Ylitalo et al (1976) and Klockowski and Levy (1987) described the collection of CSF from the cisterna magna of anesthetized rats via percutaneous puncture.…”

Section: Introductionmentioning

confidence: 99%

Development of a Percutaneous Cerebrospinal Fluid Collection Technique in F-344 Rats and Evaluation of Cell Counts and Total Protein Concentrations

et al. 2006

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A simple technique for cerebrospinal fluid (CSF) collection was developed in F-344 rats. Cell counts and total protein concentrations were evaluated to assess sample quality. While the 50 to 70 µL samples of CSF collected on three different days showed a progressive decrease in the total erythrocyte and nucleated cell counts, no significant changes were observed in the total protein concentrations. Progressive decreases in the total erythrocyte count correlated positively with the decreases in volume of CSF collected. Our data suggest that collection of less than 50 µL of CSF will give a better quality of CSF in F-344 rats. This is the first report of cellular and protein parameters in the CSF of F-344 rats.

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“…Time (h) (Danhof & Levy, 1984;Dingemanse et al, 1987;Klockowski & Levy, 1988;Sokomba et al, 1988), studies of the interrelationship between CSF and blood kinetics are desirable. The technique for the serial and simultaneous sampling of CSF and blood compartments in freely behaving rats has been found to be useful for the evaluation of the antiepileptic drug, milacemide, as much useful kinetic data was obtained on a small number of rats.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, we have used a procedure based on earlier CSF studies (Hutson et al, 1985;Sokomba et al, 1988) 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4, 5, 6, 7 and 8 h later for milacemide, glycinamide and glycine determination. CSF samples were collected in 0.5 ml polypropylene tubes, (Treff Lab, Dagersheim, Switzerland) and blood samples in 1.5 ml polypropylene tubes (Bio-Medical Laboratories Supplies, Birmingham, UK).…”

Section: Introductionmentioning

confidence: 99%

Antiepileptic drug pharmacokinetics and neuropharmacokinetics in individual rats by repetitive withdrawal of blood and cerebrospinal fluid: milacemide

Semba

Curzon

Patsalos

1993

British J Pharmacology

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The kinetics and metabolism of milacemide have been studied in an animal model which allows the simultaneous investigation of the temporal inter‐relationships of drugs and metabolites in blood (pharmacokinetics) and cerebrospinal fluid (CSF, neuropharmacokinetics) in individual freely moving rats. Milacemide dose‐dependently increased CSF glycine and glycinamide (intermediary metabolite) concentrations. This confirms that milacemide is a CNS glycine prodrug. Pretreatment with l‐deprenyl (2 mg kg−1), a specific inhibitor of monoamine oxidase type B (MAO‐B), almost completely prevented the formation of glycinamide and increased milacemide accumulation in CSF. Tmax and t1/2 were significantly increased and Cmax and AUC values were decreased for glycinamide compared to controls. Pretreatment with clorgyline (5 mg kg−1), a specific inhibitor of MAO‐type A, only moderately decreased glycinamide Cmax and AUC values. After milacemide administration (100, 200 and 400 mg kg−1, i.p.) serum and CSF milacemide concentrations rose linearly and dose‐dependently. Serum glycinamide concentrations exhibited small dose‐dependent rises but these were not linearly related. In contrast, CSF glycinamide concentrations rose linearly and dose‐dependently with Cmax values 2.5, 3.2 and 4.1 times greater than the corresponding values for serum glycinamide after giving 100, 200 and 400 mg kg−1 respectively of milacemide. Serum glycine concentrations were unaffected but CSF concentrations increased dose‐dependently and these were significant at the higher milacemide doses (200 and 400 mg kg−1). Animals given 400 mg kg−1 milacemide had glycine values which were still significantly elevated 7 h later. In conclusion, serum milacemide rapidly enters and equilibrates with the CNS compartment where it is metabolised primarily by MAO‐B to glycinamide and finally to glycine. Metabolism in the peripheral compartment is negligible.

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Concurrent monitoring of central carbamazepine and transmitter amine metabolism and motor activity in individual unrestrained rats using repetitive withdrawal of cerebrospinal fluid

Cited by 22 publications

References 17 publications

Relationship Between Exposure and Nonspecific Binding of Thirty-Three Central Nervous System Drugs in Mice

Relationship Between Exposure and Nonspecific Binding of Thirty-Three Central Nervous System Drugs in Mice

Development of a Percutaneous Cerebrospinal Fluid Collection Technique in F-344 Rats and Evaluation of Cell Counts and Total Protein Concentrations

Antiepileptic drug pharmacokinetics and neuropharmacokinetics in individual rats by repetitive withdrawal of blood and cerebrospinal fluid: milacemide

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