Pharmacodynamics of salmon calcitonin in humans: new markers of pharmacological activity.
In order to define the pharmacodynamic profile of salmon calcitonin (sCT) in humans, several markers of the biological activity of the drug have been studied, namely cAMP, adenosine and pO2 in venous blood, and the cytosolic free calcium level in circulating cells. Different dosages and routes of administration (1.5 IU.kg-1 and 0.75 IU kg-1 IM, and 1.5 IU.kg-1 via nasal spray) were compared. sCT caused an increase in cAMP, adenosine and pO2, and a decrease in cytosolic free calcium in neutrophils, lymphocytes and platelets. The peak times of all these parameters ranged between 109 and 182 min, and 101 and 168 min after IM and nasal spray administration respectively. There was greater variability in the values after IM than nasal spray of administration of sCT. It is concluded that adenosine and pO2 in venous blood, and cytosolic free calcium in circulating cells are valuable markers of the activity of sCT and that sCT decreases the cytosolic free calcium level in neutrophils, lymphocytes and platelets. Pharmacodynamic analysis of the biological effects of the drug is highly reliable and valuable in predicting its pharmacological profile. sCT administration via a nasal spray is able to produce significant biological effects, although they are less marked than after IM dosing.
Di Perri
T
T
Department of Internal Medicine, University of Siena School of Medicine, Italy.
Laghi Pasini
F
F
Capecchi
P L
PL
Blardi
P
P
Pasqui
A L
AL
Franchi
M
M
Mazza
S
S
Sodi
N
N
Domini
L
L
Ceccatelli
L
L
D000241:Adenosine / Q000097:blood; D015415:Biomarkers; D002116:Calcitonin / Q000493:pharmacokinetics*; D000242:Cyclic AMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects
D015415:Biomarkers; C028815:salmon calcitonin; D002116:Calcitonin; D000242:Cyclic AMP; D000241:Adenosine