Intrapulmonary drug delivery of salmon calcitonin.
Calcitonin (CT) and other bone-active peptides have been restrained in clinical use by the need for parenteral administration. Although nasal and other transmucosal routes can be used for CT treatment, bioavailability and bioactivity of the peptide thus delivered are limited. We have evaluated the intrapulmonary route (IP) for the delivery of salmon calcitonin (SCT) in normal subjects. SCT was administered with a dry powder delivery inhaler. For comparison, each subject also received intramuscular (IM) SCT. Inhaled SCT produced significant hypocalcemia in all subjects as did injected SCT, and the peptide could be readily measured in serum by immunoassay. Compared by dose, IP SCT had 66% of the bioactivity and 28% of the bioavailability of IM SCT. This intrapulmonary route of administration should enhance the clinical acceptability of SCT and could also be applicable to other bone-active peptides.
Deftos
L J
LJ
Department of Medicine, University of California, San Diego, CA, USA.
Nolan
J J
JJ
Seely
B L
BL
Clopton
P L
PL
Cote
G J
GJ
Whitham
C L
CL
Florek
L J
LJ
Christensen
T A
TA
Hill
M R
MR
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D001682:Biological Availability; D002116:Calcitonin / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D002118:Calcium / Q000097:blood*; D016503:Drug Delivery Systems; D005240:Feasibility Studies; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D012016:Reference Values
D000700:Analgesics; C028815:salmon calcitonin; D002116:Calcitonin; D002118:Calcium