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The use of microdialysis for the study of drug kinetics: some methodological considerations illustrated with antipyrine in rat frontal cortex
Author(s) -
Patsalos P.N.,
Abed W.T.,
Alavijeh M.S.,
O'Connell M.T.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb16362.x
Subject(s) - microdialysis , sampling (signal processing) , chemistry , sampling interval , blood sampling , kinetics , sampling time , volume (thermodynamics) , dialysis , pharmacokinetics , cortex (anatomy) , chromatography , analytical chemistry (journal) , statistics , mathematics , extracellular , surgery , medicine , biology , biochemistry , thermodynamics , neuroscience , physics , quantum mechanics , detector , optics
1 The neuropharmacokinetics of antipyrine, a readily dialysable drug, in rat frontal cortex were studied and the effect of sampling time and contribution of period sampling and dialysate dead volume investigated in relation to t max , C max , AUC and t 1/2 values. 2 After i.p. administration, antipyrine (35 mg kg −1 , n = 5) concentrations rose rapidly in rat frontal cortex ( t max , 12 min) and then declined exponentially. t max , C max , AUC and t 1/2 values were determined after 2 min dialysate sampling and compared to values obtained from simulated sampling times of 4, 6 , 8, 10 and 20 min. 3 Antipyrine t max and C max values were directly dependent on sampling frequency. Thus, mean 2 min sampling t max and C max values were 63% lower and 27% higher, respectively, compared to 20 min sampling values. AUC and t 1/2 values were unaffected. 4 Adjustment for dialysate dead volume (the volume of dialysate within the dialysis probe and sampling tube) reduced t max values significantly but did not affect the other neuropharmacokinetic parameters. 5 Contribution of period sampling on neuropharmacokinetic parameters were investigated by comparing plots of antipyrine concentration data at midpoint and at endpoint of sampling time interval. Only t max values were affected with values decreasing with increasing sampling time interval. 6 In conclusion, although microdialysis is a useful method for monitoring events at the extracellular level and for kinetic studies, it is important to understand its inherent characteristics so that data can be interpreted appropriately. Sampling frequency, particularly during monitoring of periods of rapid change, is very important since C max and t max values will be significantly underestimated and overestimated respectively, if sampling time is longer rather than shorter. These considerations are particularly important in relation to microdialysis studies of pharmacokinetic‐pharmacodynamic interrelationships and modelling.