On the absorption of drugs using chronic dog ileal loop method.
The absorption rate of three model drugs, i.e., pentacaine (highly lipophilic), stobadine (moderately lipophilic) and acetylsalicylic acid (hydrophilic), was studied using the chronic dog ileal loop method. The drugs were dissolved either in 0.9% unbuffered solution of NaCl or in antacid mixture. When using 0.9% NaCl, the half-lives of absorption (t1/2 (dis)) of pentacaine and stobadine were (mean +/- SD) 23.2 +/- 7.8 min and 20.8 +/- 7.2 min, respectively. For stobadine a good agreement was found between its t1/2 (dis) from the ileum and its absorption half-life determined from blood concentrations after oral administration to dogs. The absorption of acetylsalicylic acid accounted for only 10-20% of the dose introduced into the loop over 45 min; thus, a reliable value of t1/2 (dis) could not be determined. The administration of unbuffered solution of NaCl into the loop was accompanied by rapid increase of pH from acidic to basic value. The antacid mixture failed to affect the absorption rate of the drugs studied. Sampling from the ileum was limited to 35-55 min due to rapid absorption of water. These results suggest that: 1) measurement of the absorption rate of some drugs, e.g., stobadine, by using the chronic dog ileal loop method may adequately predict their absorption rate after peroral administration to the dog, 2) interactions of antacids with drug absorption in the ileum may not play a significant role because of the strong buffering capacity of the ileum, and 3) rapid absorption of water from the ileum does not allow to reliably determine the value of t1/2 (dis) for slowly absorbed drugs.
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava.
M
M
Kukan
S
S
Bezek
T
T
Trnovec
I
I
Gabauer
J
J
Styk
D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001241:Aspirin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002219:Carbamates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002243:Carbolines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004285:Dogs; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D007082:Ileum / Q000378:metabolism; D007408:Intestinal Absorption; D008297:Male
D000897:Anti-Ulcer Agents; D000975:Antioxidants; D002219:Carbamates; D002243:Carbolines; C010618:pentacaine; D001241:Aspirin; C100106:dicarbine