Document Detail

Effect of injection routes on pharmacokinetics and lactone/carboxylate equilibrium of 9-Nitrocamptothecin in rats.
MedLine Citation:
PMID:  17446016     Owner:  NLM     Status:  MEDLINE    
Pharmacokinetics and lactone/carboxylate equilibrium of 9-Nitrocamptothecin (9-NC) were compared after intravenous (i.v.) and intramuscular (i.m.) injection at a dose of 1.5mg/kg 9-NC solution. The concentrations of three different forms of 9-NC, namely lactone, carboxylate and total 9-NC, were measured by HPLC analysis. Injection routes were demonstrated to have significant effect on pharmacokinetics of 9-NC. Compared with i.v. injection route, mean residence time (MRT) of 9-NC three forms was significantly prolonged following i.m. route (p<0.05). The AUC(0-infinity) ratios of i.m. to i.v. route were calculated to be 102+/-43%, 273+/-221% and 150+/-62% for lactone, carboxylate and total 9-NC, respectively. Compared with i.v. injection route, although AUC(0-infinity) was barely changed, MRT of lactone 9-NC was dramatically prolonged 4.5-fold after i.m. injection, which may account for the reported improved antitumor efficacy. However, the results of the present study also demonstrated that i.m. injection route increased both AUC(0-infinity) and MRT of carboxylate 9-NC more significantly. Since the carboxylate form of CPT analogs including 9-NC is associated with their unwanted toxicity, i.m. injection route might lead to severe toxicity compared with i.v. route. Lactone/carboxylate equilibrium was also significantly influenced by injection routes. Based on the AUC(0-infinity) measurements, the lactone 9-NC constituted 50+/-8% and 32+/-7% of circulating total 9-NC after i.v. or i.m. administration, respectively (p<0.01).
Jun Chen; Qineng Ping; Jianxin Guo; Minling Liu; Baochang Cai
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2007-03-12
Journal Detail:
Title:  International journal of pharmaceutics     Volume:  340     ISSN:  0378-5173     ISO Abbreviation:  Int J Pharm     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-07-16     Completed Date:  2007-10-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7804127     Medline TA:  Int J Pharm     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  29-33     Citation Subset:  IM    
College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029, People's Republic of China.
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MeSH Terms
Antineoplastic Agents, Phytogenic / administration & dosage*,  pharmacokinetics*
Area Under Curve
Camptothecin / administration & dosage,  analogs & derivatives*,  pharmacokinetics
Carboxylic Acids / metabolism*
Chromatography, High Pressure Liquid
Injections, Intramuscular
Injections, Intravenous
Lactones / metabolism*
Rats, Sprague-Dawley
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Carboxylic Acids; 0/Lactones; 104195-61-1/9-nitrocamptothecin; 7689-03-4/Camptothecin

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