|Budget Amount *help
¥7,000,000 (Direct Cost : ¥7,000,000)
Fiscal Year 1995 : ¥2,600,000 (Direct Cost : ¥2,600,000)
Fiscal Year 1994 : ¥4,400,000 (Direct Cost : ¥4,400,000)
In the present study, the significance of the diurnal fluctuation of Ca metabolism, especially of the bone resorbing activity in rats, was discussed in relation to the administration of blockers of bone resorption. Under physiological condition, serum Ca, Ca transfer into bone and Ca release from bone followed diurnal rhythms in rats. The magnitude of the effects of blockers of bone resorption also varied diurnally depending on the time of drug administration, which indicates that the sensitivity of the target site (bone resorption process) to the drug also varied diurnally. Thus, it appears that if a blocker of bone resorption is administered during active bone resorption, it has a large effect, and if it is given during a period of less active bone resorption, its effect is diminished. In the field of Ca metabolism, the timing of drug administration or experimental method has thus far been based more frequently on the traditional homeostatic hypothesis. The homeostatic hypothesis implies that the pharmacological and toxicological effects of chemical agents are uniform, and are independing of the timing of administration. However, the studies described here have shown that this hypothesis may be invarid or inappropriate. The present findings should prove to be important not only in future experimental design and in the interpretation of experimental data, but also in the efficacious use of drugs which affect bone resorption.