Absorption of human calcitonin across the rat colon in vivo.
1. We studied the absorption of human calcitonin across the colon of juvenile female rats in vivo. Both pharmacokinetic and pharmacodynamic parameters were monitored to measure absorption. 2. Intracolonically administered human calcitonin at doses of 0.1-5.0 mg/kg resulted in a dose-dependent reduction in plasma calcium levels. 3. The bioavailability of intracolonically administered human calcitonin at doses of 5.0, 1.0 and 0.1 mg/kg was 0.5%, 0.9% and 0.2%, respectively. 4. Immunohistochemistry showed that human calcitonin transport across the rat colon was rapid and that a significant amount was via a transcellular pathway. 5. We conclude that human calcitonin crosses the gastrointestinal tract of rats in significant amounts and that this demonstrates the feasibility of an oral form for clinical use.
Hastewell
J
J
Drug Preformulation and Delivery, Ciba-Geigy Pharmaceuticals, Horsham, West Sussex, U.K.
Lynch
S
S
Williamson
I
I
Fox
R
R
Mackay
M
M
D000818:Animals; D001682:Biological Availability; D002116:Calcitonin / Q000097:blood / Q000493:pharmacokinetics*; D002118:Calcium / Q000097:blood; D003106:Colon / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007408:Intestinal Absorption; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D002116:Calcitonin; D002118:Calcium