Pharmacokinetics and Biodistribution Study of Paclitaxel Liposome in Sprague-Dawley Rats and Beagle Dogs by Liquid Chromatography-Tandem Mass Spectrometry

X. Wang; L. Song; N. Li; Z. Qiu; S. Zhou; C. Li; J. Zhao; H. Song; X. Chen

doi:10.1055/s-0033-1349126

Drug Research, Table of Contents

Drug Res (Stuttg) 2013; 63(11): 603-606
DOI: 10.1055/s-0033-1349126

Original Article

Pharmacokinetics and Biodistribution Study of Paclitaxel Liposome in Sprague-Dawley Rats and Beagle Dogs by Liquid Chromatography-Tandem Mass Spectrometry

X. Wang

¹Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China

,

L. Song

¹Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China

,

N. Li

¹Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China

,

Z. Qiu

¹Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China

,

S. Zhou

¹Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China

,

C. Li

¹Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China

,

J. Zhao

¹Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China

,

H. Song

¹Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China

,

X. Chen

¹Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China

› Author Affiliations

Abstract

Lipusu is the first paclitaxel liposome preparation approved in the world and has been widely used in China for the treatment of ovary, breast and non-small cell lung cancer. In present study we evaluated the pharmacokinetic and tissue distribution characteristics of paclitaxel liposome in Sprague-Dawley rats and Beagle dogs. A rapid and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed for the determination of paclitaxel in plasma and tissues. The plasma concentrations of paclitaxel in both rats and dogs initially declined steeply, followed by slow elimination after intravenous administration of Lipusu at 5 mg/kg and 1 mg/kg, respectively. The pharmacokinetic parameters calculated by a non-compartmental method in rats and dogs were as follows: AUC_0–24: 3 566.5±1 366.1 and 443.2±165.7 μg · h/L, CL: 1.5±0.5 and 2.1±0.6 L/h/kg, V_d: 20.0±7.8 and 38.4±12.5 L/kg, t_1/2: 9.3±2.9 and 14.1±6.9 h, respectively. Biodistribution results in rats showed that except for brain and testis, liposomal paclitaxel was extensively distributed into various tissues, especially highly in liver and spleen.

Key words

lipusu - disposition - in vivo - LC-MS/MS

Full Text

References

References
1 Crown J, O’Leary M. The taxanes: an update. Lancet 2000; 355: 1176-1178
2 Dorr RT. Pharmacology and toxicology of Cremophor EL diluent. Ann Pharmacother 1994; 28: S11-S114
3 Szebeni J, Muggia FM, Alving CR. Complement activation by Cremophor EL as a possible contributor to hypersensitivity to paclitaxel: an in vitro study. J Natl Cancer Inst 1998; 90: 300-306
4 Mass B, Huber C, Krämer I. Plasticizer extraction of Taxol infusion solution from various infusion devices. Pharm World Sci 1996; 18: 78-82
5 Miele E, Spinelli GP, Miele E et al. Albumin-bound formulation of paclitaxel (Abraxane ABI-007) in the treatment of breast cancer. Int J Nanomedicine 2009; 4: 99-105
6 Nornoo AO, Osborne DW, Chow DS. Cremophor-free intravenous microemulsions for paclitaxel I: formulation, cytotoxicity and hemolysis. Int J Pharm 2008; 349: 108-116
7 Mita AC, Olszanski AJ, Walovitch RC et al. Phase I and pharmacokinetic study of AI-850, a novel microparticle hydrophobic drug delivery system for paclitaxel. Clin Cancer Res 2007; 13: 3293-3301
8 Kim SC, Kim DW, Shim YH et al. In vivo evaluation of polymeric micellar paclitaxel formulation: toxicity and efficacy. J Control Release 2001; 72: 191-202
9 Koudelka S, Turánek J. Liposomal paclitaxel formulations. J Control Release 2012; 163: 322-334
10 Fetterly GJ, Grasela TH, Sherman JW et al. Pharmacokinetic/pharmacodynamic modeling and simulation of neutropenia during phase I development of liposome-entrapped paclitaxel. Clin Cancer Res 2008; 14: 5856-5863
11 Schuch G. EndoTAG-1. MediGene. Curr Opin Investig Drugs 2005; 6: 1259-1265
12 Wang H, Cheng G, Du Y et al. Hypersensitivity reaction studies of a polyethoxylated castor oil-free, liposome-based alternative paclitaxel formulation. Mol Med Rep 2013; 7: 947-952
13 Chen Q, Zhang QZ, Liu J et al. Multi-center prospective randomized trial on paclitaxel liposome and traditional taxol in the treatment of breast cancer and non-small-cell lung cancer. Zhonghua Zhong Liu Za Zhi 2003; 25: 190-192
14 Zhang Q, Huang XE, Gao LL. A clinical study on the premedication of paclitaxel liposome in the treatment of solid tumors. Biomed Pharmacother 2009; 63: 603-607
15 Alexander MS, Kiser MM, Culley T et al. Measurement of paclitaxel in biological matrices: high-throughput liquid chromatographic-tandem mass spectrometric quantification of paclitaxel and metabolites in human and dog plasma. J Chromatogr B Analyt Technol Biomed Life Sci 2003; 785: 253-261
16 Kim SC, Yu J, Lee JW et al. Sensitive HPLC method for quantitation of paclitaxel (Genexol in biological samples with application to preclinical pharmacokinetics and biodistribution. J Pharm Biomed Anal 2005; 39: 170-176
17 Guo P, Ma J, Li S et al. Determination of paclitaxel in mouse plasma and brain tissue by liquid chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2003; 798: 79-86
18 Sottani C, Minoia C, D’Incalci M et al. High-performance liquid chromatography tandem mass spectrometry procedure with automated solid phase extraction sample preparation for the quantitative determination of paclitaxel (Taxol) in human plasma. Rapid Commun Mass Spectrom 12: 251-255
19 Fetterly GJ, Straubinger RM. Pharmacokinetics of paclitaxel-containing liposomes in rats. AAPS PharmSci 2003; 5: E32