Evaluation of colonic absorbability of drugs in dogs using a novel colon-targeted delivery capsule (CTDC).
A series of dog studies were performed to examine the in vitro/in vivo relationship of drug release behavior of the newly developed colon-targeted delivery capsule (CTDC). The four kinds of CTDCs containing theophylline, each of which has a different in vitro dissolution lag time, were orally administered to four beagle dogs under fasted condition, and the onset times of drug absorption were compared. The CTDC with longer in vitro lag time had a later onset of drug absorption. It was also found that the time difference between the gastric emptying and the onset of drug absorption was almost equal to the in vitro dissolution lag time of the capsule, suggesting a similar performance of CTDC in the gastrointestinal tract. From the comparison to the absorption behavior of the colon arrival marker, i.e. sulfasalazine, it was proved that the CTDC with the lag time of 3 h can deliver the drug directly to the colon. This result implied that the CTDC can be used as a non-invasive means for assessing the regional absorbability of drugs in the gastrointestinal tract. To evaluate the absorbability of drugs in the colon, three model drugs, theophylline (THEO), acetaminophen (ACET), and phenylpropanolamine hydrochloride (PPA) were directly delivered to the colons of beagle dogs using the CTDC with the lag time of about 3 h. The obtained relative bioavailabilities to the solution form were as high as 94.2%, 71.0%, and 91.5% for THEO, ACET and PPA, respectively, suggesting that the colonic absorbability of those drugs is essentially good.
Ishibashi
T
T
Pharmaceutics Research Laboratory, Tanabe Seiyaku Co., Ltd., 16-89, Kashima 3-chome, Yodogawa-ku, Osaka 532, Japan. ryu-i@tanebe.co.jp
Ikegami
K
K
Kubo
H
H
Kobayashi
M
M
Mizobe
M
M
Yoshino
H
H
D000042:Absorption; D000082:Acetaminophen / Q000097:blood / Q000737:chemistry; D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D002214:Capsules / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003106:Colon / Q000378:metabolism*; D004285:Dogs; D005215:Fasting; D005746:Gastric Emptying; D066298:In Vitro Techniques; D008297:Male; D009928:Organ Specificity; D010665:Phenylpropanolamine / Q000493:pharmacokinetics; D012460:Sulfasalazine / Q000493:pharmacokinetics; D013806:Theophylline / Q000097:blood* / Q000737:chemistry; D013997:Time Factors
D002214:Capsules; D010665:Phenylpropanolamine; D000082:Acetaminophen; D012460:Sulfasalazine; D013806:Theophylline