Validation of Microdialysis Sampling for Subcutaneous Extracellular Valproic Acid in Humans

Lindberger, Martin; Tomson, Torbjörn; Ståhle, Lars

doi:10.1097/00007691-199806000-00020

Cited by 21 publications

(17 citation statements)

References 13 publications

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“…8,9 Subcutaneous tissue is an attractive sampling site for several reasons: 1. this tissue is relatively uniform, 2. the extracellular¯uid is in constant¯ux with the systemic circulation, and 3. the implantation of the probe in sc tissue is easy. 7 Despite these interesting characteristics, no data are reported in the literature regarding the use of sc microdialysis sampling to study the pharmacokinetics of drugs with a very high plasma protein binding in the awake freely moving rat.…”

Section: ±5mentioning

confidence: 99%

Validation of subcutaneous microdialysis sampling for pharmacokinetic studies of flurbiprofen in the rat

Mathy¹,

Préat²,

Verbeeck³

2001

J. Pharm. Sci.

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The objective of this study was to validate subcutaneous (sc) microdialysis sampling to study¯urbiprofen pharmacokinetics and plasma protein binding in the awake freely moving rat. A linear microdialysis probe was manufactured using a Hemophane 1 hollow ®ber which was tested in vitro and in vivo for the recovery of urbiprofen and naproxen used as retrodialysis marker. Flurbiprofen was administered intraperitoneally and intravenously at a dose of 20 mg/kg in rats. In both cases, conventional blood sampling and sc microdialysis sampling were simultaneously performed. The microdialysates were analyzed on-line by high-pressure liquid chromatography. Naproxen, which was shown to have a similar in vivo loss by retrodialysis as¯urbiprofen (71.5 AE 0.9% and 71.0 AE 0.8% respectively, n 3), was used to continuously monitor probe recovery. Concentration-dependent protein binding of urbiprofen was demonstrated in vivo based on experiments with a simultaneous sc microdialysis and blood sampling. Values of unbound fraction were similar to those reported previously by intravenous microdialysis sampling, demonstrating that the sc unbound concentrations are very similar to those in the central compartment. There was no signi®cant difference among pharmacokinetic parameters (AUC, CL, t 1/2z , Vd) for total or unbound¯urbiprofen determined after intraperitoneal and intravenous administration. Subcutaneous microdialysis is a simple yet powerful tool to study the pharmacokinetics and the in vivo plasma protein binding of¯urbiprofen in the awake unrestrained rat. ß

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Section: ±5mentioning

confidence: 99%

Validation of subcutaneous microdialysis sampling for pharmacokinetic studies of flurbiprofen in the rat

Mathy¹,

Préat²,

Verbeeck³

2001

J. Pharm. Sci.

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“…The insertion of microdialysis probes was not perceived due to the use of local anaesthesia. Microdialysis probes can be inserted in the dermis without anaesthesia, and the discomfort is similar to what is perceived during ordinary blood sampling (5,14).…”

Section: Discussionmentioning

confidence: 99%

“…The technique has the advantage of being minimally invasive when applied to sampling in the skin, and it provides highly reproducible real-time chronological sampling with a short time resolution. The tolerability of microdialysis sampling is high, and pharmacokinetic studies of up to 3 days duration have been performed in patients (5). Microdialysis samples extracellular uid in the tissue in which the probe is placed, but excludes larger molecules and proteins from the sample.…”

mentioning

confidence: 99%

Microdialysis vs. Suction Blister Technique for In vivo Sampling of Pharmacokinetics in the Human Dermis

Benfeldt

Serup²,

Menné³

1999

Acta Dermato-Venereologica

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Our aim was to simultaneously investigate 2 techniques for in vivo sampling of peripheral compartment pharmacokinetics after systemic administration of acetylsalicylic acid. Ten volunteers were given 2 g acetylsalicylic acid orally. Blood samples and dialysates from 4 microdialysis probes inserted in the dermis of the forearm were collected for 5 h and suction blisters were raised 1-3 h after dosing. In microdialysates, both acetylsalicylic acid and the metabolite salicylic acid were measurable in the absence of hydrolysing enzymes. The mean Cmax (maximum concentration) of total, unbound salicylic acid was 9.5 microg/ml in microdialysates, 13.2 microg/ml in suction blister fluid and 56.5 microg/ml in plasma. Mean Tmax (time to Cmax) for salicylic acid was 188 and 161 min in plasma and microdialysates, respectively. The dermis-to-plasma Cmax ratio was 0.16+/-0.04 (mean +/- SD) by microdialysis sampling and 0.25+/-0.09 by the suction blister fluid method. Close correlations (p<0.01) were found between Cmax of salicylic acid in microdialysates and plasma, and between Cmax of salicylic acid in suction blister fluid and plasma. The 2 techniques were in excellent accordance with even closer correlation between maximum concentrations obtained by microdialysis and suction blister fluid sampling (p<0.001). However, comparing the tolerability of the sampling procedure, ease of analysis, and detail in chronology, microdialysis is superior for sampling in vivo pharmacokinetics in the dermis.

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“…Implantation of CMA20/10 probes in the abdominal skin area was performed as described in earlier reports (Lindberger et al, 1998; Graumlich et al, 2000; Mathy et al, 2001) and samples times were synchronized along with brain samples times. After implantation, the probes were perfused with Ringer’s solution for 40 min before either intravenous or unilateral nasal administration.…”

Section: Methodsmentioning

confidence: 99%

Nose-to-brain transport of melatonin from polymer gel suspensions: a microdialysis study in rats

Babu

Dayal²,

Pawar

et al. 2011

Journal of Drug Targeting

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Purpose Exogenous melatonin (MT) has significant neuroprotective roles in Alzheimer’s and Parkinson’s diseases. This study investigates the delivery MT to brain via nasal route as a polymeric gel suspension using central brain microdialysis in anesthetized rats. Methods Micronized MT suspensions using polymers [carbopol, carboxymethyl cellulose (CMC)] and polyethylene glycol 400 (PEG400) were prepared and characterized for nasal administration. In vitro permeation of the formulations was measured across a three-dimensional tissue culture model EpiAirway™. The central brain delivery into olfactory bulb of nasally administered MT gel suspensions was studied using brain microdialysis in male Wistar rats. The MT content of microdialysis samples was analyzed by high performance liquid chromatography (HPLC) using electrochemical detection. The nose-to-brain delivery of MT formulations was compared with intravenously administered MT solution. Results MT suspensions in carbopol and CMC vehicles have shown significantly higher permeability across Epiairway™ as compared to control, PEG400 (P < 0.05). The brain (olfactory bulb) levels of MT after intranasal administration were 9.22, 6.77 and 4.04-fold higher for carbopol, CMC and PEG400, respectively, than that of intravenous MT in rats. In conclusion, microdialysis studies demonstrated increased brain levels of MT via nasal administration in rats.

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Validation of Microdialysis Sampling for Subcutaneous Extracellular Valproic Acid in Humans

Cited by 21 publications

References 13 publications

Validation of subcutaneous microdialysis sampling for pharmacokinetic studies of flurbiprofen in the rat

Validation of subcutaneous microdialysis sampling for pharmacokinetic studies of flurbiprofen in the rat

Microdialysis vs. Suction Blister Technique for In vivo Sampling of Pharmacokinetics in the Human Dermis

Nose-to-brain transport of melatonin from polymer gel suspensions: a microdialysis study in rats

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