[Study on pharmacokinetics of HCPT nanosuspensions with ability of inhibiting P-gp in rats after oral administration].
OBJECTIVE
To study on pharmacokinetics of hydroxycamptothecine (HCPT) nanosuspensions in rats after oral administration.


METHODS
The plasma concentrations of HCPT were determined by HPLC-FD. The analysis was performed on a diamonsil C18 column (4.6 mm x 200 mm, 5 microm) with 0.3% acetic acid-triethylamine buffer (pH 5.0) and methanol (57: 43) as mobile phase. The flow rate was 1.0 mL x min(-1); the excitation wave was set at 363 nm, and emission wave was set at 550 nm; the temperature was 35 degrees C. All data of concentration-time of HCPT were treated with pharmacokinetics program DAS 2.0.


RESULTS
The concentration-peak area of this assay had a good linear relation in the range from 1 to 50 microg x L(-1), and the minimum limit of quantitation was 1 microg x L(-1). The inter- and intra-day precisions of HCPT were smaller than 4.3%, and the accuracy were between -5.59% and 5.59%. The recoveries of HCPT in three plasma concentrations including high, medial, low concentration were 98.94%, 95.88% and 102.69%, respectively, which was in line with the request of biopharmaceutical analysis. The plasma concentration time profiles of HCPT fitted in two-compartment models well, and the main pharmacokinetic parameters found for HCPT after oral administration were as follows: Cmax 13.10 microg x L(-1), Tmax 0.75 h, t(1/2alpha) 8.242 h, t(1/2beta) 136.122 h, AUC(0-t) 116.77 microg x h x L(-1), AUC(0-infinity) 161.93 microg x h x L(-1).


CONCLUSIONS
The HPLC-FD method was simple, with good specificity, reproducibility, and could be used to investigate the pharmacokinetics and determinate the concentration of hydroxycamptothecin. The nanosuspension in this study could accelerate the oral absorption rate of HCPT, and make improving bioavailability of HCPT possible.
Pharmaceutical College of Henan University, Kaifeng 475004, China. pgh425@163.com
Xiaohui
X
Pu
Jin
J
Sun
Peng
P
Zhang
Yongjun
Y
Wang
Yinghua
Y
Sun
Zhonggui
Z
He
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000284:Administration, Oral; D000818:Animals; D002138:Calibration; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016014:Linear Models; D008297:Male; D049329:Nanostructures; D051381:Rats; D017208:Rats, Wistar; D013535:Suspensions
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D013535:Suspensions; C028098:10-hydroxycamptothecin; D002166:Camptothecin