Pharmacokinetics of cyclophosphamide after oral and intravenous administration to dogs with lymphoma.

Abstract

BACKGROUND: Cyclophosphamide is an alkylating chemotherapeutic drug administered i.v. or p.o.. 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 p.o. or i.v.. ANIMALS: Sixteen client-owned dogs with substage A lymphoma were enrolled in the study. Eight dogs received cyclophosphamide i.v. and 8 received it p.o.. 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 &#xb1; 3.77 &#x3bc;g/h/mL) compared with exposure after oral administration (P-value < .05). No difference in drug exposure to 4-OHCP was detected after i.v. (1.66 &#xb1; 0.36 &#x3bc;g/h/mL) or p.o. (1.42 &#xb1; 0.64 &#x3bc;g/h/mL) administered cyclophosphamide. CONCLUSIONS AND CLINICAL IMPORTANCE: Drug exposure to the active metabolite 4-OHCP is equivalent after administration of cyclophosphamide either p.o. or i.v..