PHARMACODYNAMICS OF SALMON-CALCITONIN IN HUMANS - NEW MARKERS OF PHARMACOLOGICAL ACTIVITY

被引:7
作者
DIPERRI, T [1 ]
PASINI, FL [1 ]
CAPECCHI, PL [1 ]
BLARDI, P [1 ]
PASQUI, AL [1 ]
FRANCHI, M [1 ]
MAZZA, S [1 ]
SODI, N [1 ]
DOMINI, L [1 ]
CECCATELLI, L [1 ]
VOLPI, L [1 ]
机构
[1] UNIV SIENA,SCH MED,DEPT INTERNAL MED,I-53100 SIENA,ITALY
关键词
SALMON CALCITONIN; PHARMACODYNAMICS; ADENOSINE; PO2; IM DOSING; NASAL SPRAY DOSING; CYTOSOLIC CALCIUM; NEUTROPHILS; PLATELETS; LYMPHOCYTES;
D O I
10.1007/BF02333015
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:229 / 233
页数:5
相关论文
共 28 条
[1]  
AZRIA M, 1989, CALCITONINS PHYSL PH, P1
[2]  
Becker BF, 1987, TOPICS PERSPECTIVES, P406
[3]  
BERNE RM, 1985, METHOD PHARMACOL, P331
[4]  
BORLE AB, 1983, TRIANGLE, V2, P75
[5]  
CANIGGIA A, 1987, CALCIF TISSUE RES S, V2, P318
[6]   PHARMACOLOGICAL CONTROL OF OSTEOCLASTIC MOTILITY [J].
CHAMBERS, TJ ;
DUNN, CJ .
CALCIFIED TISSUE INTERNATIONAL, 1983, 35 (4-5) :566-570
[7]  
CHRISTOPHER YP, 1985, CIRCULATION, V71, P787
[8]   ADENOSINE RECEPTORS - TARGETS FOR FUTURE DRUGS [J].
DALY, JW .
JOURNAL OF MEDICINAL CHEMISTRY, 1982, 25 (03) :197-207
[9]  
GENNARI C, 1981, CURR THER RES CLIN E, V30, P1024
[10]  
GRYNKIEWICZ G, 1985, J BIOL CHEM, V260, P3440