MUSCLE MICRODIALYSIS AS A MODEL STUDY TO RELATE THE DRUG CONCENTRATION IN TISSUE INTERSTITIAL FLUID AND DIALYSATE

The steady-state dialysis kinetics in buffer, erythrocyte suspension and muscle have been analyzed by clearance theory in the microdialysis study. "Tube" model has been demonstrated to be a useful model to relate the dialysis clearance, CL(D), the dialysis flow rate, F, and the permeability rate constant, PA, for microdialysis employing the transcranial type microdialysis probe. The effective dialysis coefficient (R(d)), defined as the ratio of the in vivo PA and in vitro PA, was introduced to account for the differences between in vivo and in vitro microdialysis. The Arrhenius plot of the antipyrine permeability rate constant presented a single straight line in the range of 15-37-degrees-C with an activation energy of 5.49 kcal/mol. A fairly good correlation was observed between the reciprocal of the permeability rate constant and the root of the molecular weight in the range of 18-1039. On the contrary, the molecular weight and the plasma membrane permeability were not determinant factors for R(d) value determined in the erythrocyte suspension (R(d,erythrocyte)), while the interstitial fluid space (100 - hematocrit)% of erythrocyte suspension plays a dominant factor to change R(d,erythrocyte). The in vivo permeability rate constant was determined in the muscle for [H-3]water, [C-14]urea, antipyrine and [C-14]sucrose under the steady-state condition. No significant difference of R(d) in muscle tissue was demonstrated for these four model substances. By using the R(d) value, a hypothetical equation has been proposed to relate the concentration in the dialysate and the interstitial fluid at steady-state.