ISSN:
1432-1912
Schlagwort(e):
Intestinal Absorption
;
Basic Drugs
;
Amidopyrine
;
Antipyrine
;
Solvent Drag
;
Rat
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Summary 1. Jejunal loops of anaesthetized rats were perfused with hypotonic, isotonic and hypertonic buffered solutions containing 14C-labelled amidopyrine and antipyrine at neutral and at acidic pH. The blood flow of the loop was maintained at an intermediate rate (0.7–1.0 ml min−1g−1). The water net flux was determined by means of polyethylene glycol as non-absorbable marker and amounted up to ±30 μl min−1g−1. 2. A positive water net flux (directed towards the blood) increased the appearance rate of amidopyrine and antipyrine by maximally 43.8 and 49.2%, a negative water net flux (directed towards the gut lumen) diminished it by 38.8 and 35.0%. 3. The experimental data were analysed by means of a kinetic model with the water net flux as independent variable and the epithelial permeability kF D , the serosal permeability k S F S and the sieving coefficient Φ=1−σ as absorption parameters. For antipyrine independent of the pH-value of the perfusion solution kF D was 0.123, and, for amidopyrine at pH 7 and pH 3 kF D was 0.231 and 0.091, respectively. k S F S was zero indicating that in this experimental arrangement the transfer of drug molecules to the serosal side was negligible. The sieving coefficient Φ amounted to 2.30 for amidopyrine and 2.15 for antipyrine at neutral pH. At acidic pH it amounted to 0.50 for amidopyrine and 1.44 for antipyrine. The hydraulic permeability of water was identical at neutral and acidic pH. 4. The high sieving coefficient for the two drugs at neutral pH is interpreted as indicating that water and lipophilic drug molecules interact within the lipid part of the cell membrane. At acidic pH the ionized drug molecules appear to permeate the cell membrane preferentially across other (presumably more hydrophilic) areas.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF00503497
