[In vitro and in vivo stability of 9-nitrocamptothecin lactone form in rats].
OBJECTIVE
To investigate the in vitro and in vivo stability of 9-nitrocamptothecin lactone form in rat plasma.


METHODS
The specific and accurate HPLC method was developed for quantifying 9-nitrocamptothecin lactone form and the total lactone and carboxylate forms simultaneously. By using of this method, the ratios of lactone form to the total in rat plasma at different time were determined in vitro and in vivo. The results were compared to determine which was the main factor influencing the stability of 9-nitrocamptothecin lactone form in rat plasma in vivo.


RESULTS
The stability of lactone form in rat plasma was much higher in vivo than that in vitro.


CONCLUSIONS
Blood cells help to increase the stability of 9-nitrocamptothecin lactone form. Clearance from blood in vivo is the primary factor which influences the plasma stability of 9-nitrocamptothecin lactone form. The kinetic process of 9-nitrocamptothecin lactone form and total drug in rats were both best fitted to a two-compartment model. However, the process of 9-nitrocamptothecin carboxylate form in vivo was best fitted to a one-compartment model.
Chen
Jun
J
Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Ping
Qi-Neng
QN
Guo
Jian-Xin
JX
Liu
Lei
L
Chu
Xiao-Zhu
XZ
Song
Ming-Mei
MM
D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D002264:Carboxylic Acids / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004355:Drug Stability; D007783:Lactones / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D007783:Lactones; C079905:rubitecan; D002166:Camptothecin