Pharmacokinetics and its relation to toxicity of pegylated-liposomal doxorubicin in Chinese patients with breast tumours.

Objectives: Pegylated liposomal doxorubicin (PLD) is a formulation of doxorubicin encapsulated with polyethylene glycol-coated liposomes, which has prolonged circulation time and unique toxicity profile. This study deals with the pharmacokinetics and its relation to toxicity in Chinese patients with breast tumours.

Methods: Twenty-two Chinese female patients with breast tumours were received two PLD products in single dose of 50 mg/m2 with a randomized, two-period and cross-over design. Blood was sampled immediately before and at 15, 30, 60 min, 1·17, 2, 5, 13, 25, 49, 73, 97, 121, 145 and 241 h after the PLD infusion. The plasma level of doxorubicin was determined with LC-MS.

Results: The pharmacokinetics of PLD was best described by a one-compartment linear structural model with a long elimination T(1/2) (64 h), a slow clearance (0·025 L/h/m2) and a small volume of distribution (2·310 L/m2). The main toxicities were neutropenia (22/44), nausea (22/44), vomiting (8/44) and pigmentation (4/44). The nausea and neutropenia were positively correlated with AUC while negatively correlated with Cl (P<0·05).

Conclusions: The study confirms the different pharmacokinetic and toxicity profiles of PLD compared with non-liposomal doxorubicin. The pharmacokinetic profiles in Chinese patients with breast tumours is different from those reported for European patients with metastatic breast cancer. The correlation between toxicities, neutropenia grade and nausea and two of the pharmacokinetic parameters, AUC and Cl, may be useful for guiding the dosing of the agent.