Clearance of cyclopentyladenosine and cyclohexyladenosine in rats following a single subcutaneous dose.
A(1)-adenosine receptor agonist N(6)-cyclopentyladenosine (CPA) (3.0 mg kg(-1) body weight), or N(6)-cyclohexyladenosine (CHA) (3.0 mg kg(-1) body weight) was subcutaneously (s.c.) administered as a single dose to rats. After that, the blood samples (150 microl) were collected from vena saphena into heparinized capillary tubes at the different time points. The concentrations of CPA and CHA were assayed by reversed-phase high performance liquid chromatography (HPLC). Based on the present study, the retention times for CPA and CHA were 3.029 +/- 0.017 min and 5.07 +/- 0.031 min, respectively. In addition, the maximum concentrations of CPA and CHA were measured 60 and 80 min after the administration, and the half-lives of these compounds in the circulation were approximately 48.5 +/- 4.4 min and 106.6 +/- 7.4 min, respectively. Presumably, the difference between these values due to the larger cycloalkyl substituent of CHA and different absorption properties of these compounds. Moreover, in the present study, the elimination half-life was approximately sevenfold longer than that previously reported for CPA (48.5 +/- 4.4 min versus 6.9 +/- 0.5] min). The discrepancy in the half-life is not surprising because the administration route was different. On the other hand, after the s.c. administration, the absorption rates of these adenosine analogues are known to be slow. Based on the results of this paper, the authors conclude that the half-life of CHA is approximately 2.2-fold compared to that of CPA.
Tuovinen
Kai
K
Department of Physiology, University of Kuopio, P.O. Box 1627, SF-70211 Kuopio, Finland. kai.tuovinen@uku.fi
Tarhanen
Juhani
J
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D006207:Half-Life; D007279:Injections, Subcutaneous; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D000241:Adenosine