Pharmacokinetics of Cyclophosphamide after Oral and Intravenous Administration to Dogs with Lymphoma

Journal of Veterinary Internal Medicine

E. Warry¹  R.J. Hansen¹  D.L. Gustafson¹ 

[1] Animal Cancer Center, Colorado State University, Fort Collins, CO

关键词: Chemotherapy;    Liquid chromatography;    Mass spectrometry;    Pharmacokinetics;   

DOI  :  10.1111/j.1939-1676.2011.0730.x

来源: Wiley

【 摘 要 】

Abstract

Background: Cyclophosphamide is an alkylating chemotherapeutic drug administered IV or PO. It is currently assumed that exposure to the active metabolite, 4-hydroxycyclophosphamide (4-OHCP), is the same with either route of administration.

Objectives:

To characterize the pharmacokinetics of cyclophosphamide and 4-OHCP in dogs with lymphoma when administered PO or IV.

Animals: Sixteen client-owned dogs with substage A lymphoma were enrolled in the study. Eight dogs received cyclophosphamide IV and 8 received it PO.

Methods: Prospective randomized clinical trial was performed. Blood was collected from each dog at specific time points after administration of cyclophosphamide. The serum was evaluated for the concentration of cyclophosphamide and 4-OHCP with mass spectrometry and liquid chromatography.

Results: Drug exposure to cyclophosphamide measured by area under the curve (AUC)_0–inf is significantly higher after intravenous administration (7.14 ± 3.77 μg/h/mL) compared with exposure after oral administration (P-value < .05). No difference in drug exposure to 4-OHCP was detected after IV (1.66 ± 0.36 μg/h/mL) or PO (1.42 ± 0.64 μg/h/mL) administered cyclophosphamide.

Conclusions and Clinical Importance: Drug exposure to the active metabolite 4-OHCP is equivalent after administration of cyclophosphamide either PO or IV.

【 授权许可】

Unknown   
Copyright © 2011 by the American College of Veterinary Internal Medicine