Influence of Vehicle on Gastrointestinal Absorption of Phenytoin in Rats

• Published in: Chemical & pharmaceutical bulletin Vol. 33; no. 11; pp. 4981 - 4988
• Main Authors: YAMANAKA, YOU, MIZUNO, NOBUYASU, HAMAGUCHI, TSUNEO, SHINKUMA, DENJI, YATA, NOBORU
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01.01.1985; 公益社団法人日本薬学会; Maruzen; Japan Science and Technology Agency
• Subjects: Animals; Anticonvulsants. Antiepileptics. Antiparkinson agents; aqueous suspension; bioavailability; Biological and medical sciences; Biological Availability; dissolution rate; Intestinal Absorption; Male; Medical sciences; Neuropharmacology; oily suspension; Pharmaceutical Vehicles; Pharmacology. Drug treatments; phenytoin; Phenytoin - blood; Phenytoin - metabolism; phenytoin solubility; rat; Rats; Rats, Inbred Strains; vehicle viscosity; Vertebrata; Mammalia; Drug vehicle interaction; Rat; Oil water emulsion; Animal; Rodentia; Anticonvulsant; Bioavailability; Aqueous solution
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.33.4981

The relationship between the bioavailability of various phenytoin (DPH) suspensions and the physicochemical properties of the vehicle as well as the physiological factors influencing the bioavailabllity were studied in rats. The vehicles used were aqueous solutions of methylcellulose (0.1, 0.5 and 1%), 1% polysorbate 80 aqueous solution, sesame oil and sesame oil emulsion. The gastric emptying time was determined from the amount of phenol red remaining in the stomach after oral administration. As the gastric emptying time increased, the area under the blood concentration-time curve, the maximum blood concentration and the time required to reach the maximum blood concentration increased. The gastric emptying time became smaller as the fluidity of the vehicle increased. Clearly, the viscosity is an important factor affecting the bioavailability of DPH. As the gastric emptying and the dissolution rate slowed down, the apparent absorption rate constant (ka) became small. However, ka obtained from an oily suspension was only one-third of the value obtained from an aqueous suspension. Thus, the mechanism by which DPH is absorbed from the digestive tract after administration as an oily suspension appears to be considerably different from that after administration as an oily suspension appears to be considerably different from that after administration as an aqueous suspension. The value of ka obtained from the in vivo absorption study was about half of that found in situ. These results suggest that ka obtained from the in vivo absorption study includes the transit rate of suspension from the stomach to the intestinal tract.