Biao Luo
<<But in order to validate their delivery technology, they
only needed to ask if Depo-oranges are better
than plain oranges?>>
I think whats below says yes.
Regards,
John
Pharmacokinetics (PK) of Depocyt™ after intrathecal administration for the treatment of leptomeningeal metastases
(LM). R. Braeckman 1, S. Phupanich2 B. Maria3, and F. Kohn4.
1Chiron Corp., Emeryville, CA, 2Moffit Cancer Center, Tampa, FL, 3University of Florida, Gainesville, FL, 4DepoTech, San Diego, CA.
The cytotoxic effect of the cell cycle phase-specific
agent cytarabine (ara-C).can be enhanced by increasing
the exposure time to allow more tumor cells to enter the S-phase. Because of the short half-life of ara-C in vivo, frequent
dosing is needed to maintain cytotoxic levels.
DepoCytO is a sterile, injectable suspension of cytarabine encapsulated into multivesicular, lipid-based particles
(DepoFoamO for sustained release. As part of a Phase III study,
the PK of ara-C was evaluated in 8 LM patients after
intraventricular or lumbar administration of 50 mg DepoCyt. Ventricular and/or lumbar cerebrospinal fluid (CSF)
and plasma samples were assayed with LC/MS/MS for free and encapsulated ara-C, and its metabolite ara-U.
Free and encapsulated CSF ara-C levels peaked
rapidly in the injection compartment,
and subsequently declined rapidly as
distribution occurred throughout the neuraxis.
Peak levels were generally 10-100 and 100-1000 mg/mL for
free and encapsulated ara-C, respectively.
After 24 hr, free and encapsulated ara-C levels
declined more slowly and were still detectable
(>0.02 mg/mL) at 7-14 days postdosing.
Plasma ara-C and ara-U concentrations
were low or undetectable, indicating minimal
systemic exposure.
Thus, drug CSF exposure was enhanced over time,
resulting in lower peak ara-C levels and longer
duration of exposure after DepoCyt administration
than would be expected
after standard ara-C delivery.
These results are consistent with earlier reports
and provide support for the
hypothesis that DepoCyt provides cytotoxic concentrations
of ara-C during the dosing intervals in the Phase III trial.
asco.org |
