PMID- 2766281
OWN - NLM
STAT- MEDLINE
DCOM- 19891003
LR  - 20131121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 49
IP  - 18
DP  - 1989 Sep 15
TI  - Controlled delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea from ethylene-vinyl 
      acetate copolymer.
PG  - 5103-7
AB  - 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) has been found to be an effective 
      chemotherapeutic agent against brain tumors. However, because it has a very short 
      half-life in plasma, the exposure of neoplastic cells to BCNU is very brief. The 
      delivery of BCNU may be enhanced by using controlled release polymers. We 
      measured the release of BCNU from ethylene-vinyl acetate copolymer (EVAc) into 
      blood, phosphate buffer, and brain tissue. BCNU-EVAc cylinders that weighed 60 mg 
      were implanted in the peritoneum of rats, and BCNU was detected in blood for 6 
      days. Studies carried out in vitro showed that BCNU was released from EVAc at a 
      decreasing rate for 195 h. BCNU-EVAc cylinders that weighed 15 mg were implanted 
      either intracranially (i.c.) or i.p. in Fischer 344 rats. Controlled release of 
      BCNU from the i.c. BCNU-EVAc implants was observed over 9 days, with peak drug 
      levels of 49.6 micrograms/g of brain tissue in the implanted hemisphere. The BCNU 
      levels in the contralateral hemisphere and the peripheral circulation were much 
      lower and were detectable for only 1 day. By contrast, peak BCNU levels in the 
      brain from the i.p. BCNU-EVAc implants were 2.7-3.0 micrograms/g for only 12 h, 
      accompanied by peak BCNU levels in blood of 1.0 micrograms/ml tapering over 1 
      day. These results demonstrate the controlled release of intact BCNU from EVAc in 
      vitro and in vivo. Furthermore, the i.c. implants resulted in localized, 
      prolonged, high levels of the drug in the implanted hemisphere. Hence, the i.c. 
      controlled delivery of BCNU may be more efficacious for the treatment of 
      localized brain tumors.
FAU - Yang, M B
AU  - Yang MB
AD  - Department of Neurological Surgery, Johns Hopkins University School of Medicine, 
      Baltimore, Maryland 21205.
FAU - Tamargo, R J
AU  - Tamargo RJ
FAU - Brem, H
AU  - Brem H
LA  - eng
GR  - NS01058-01/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Drug Implants)
RN  - 0 (Polyvinyls)
RN  - 24937-78-8 (ethylenevinylacetate copolymer)
RN  - U68WG3173Y (Carmustine)
SB  - IM
MH  - Animals
MH  - Brain/metabolism
MH  - Carmustine/*administration & dosage/blood/pharmacokinetics
MH  - Delayed-Action Preparations
MH  - Drug Implants
MH  - Half-Life
MH  - Male
MH  - *Polyvinyls
MH  - Rats
MH  - Rats, Inbred F344
EDAT- 1989/09/15 00:00
MHDA- 1989/09/15 00:01
CRDT- 1989/09/15 00:00
PHST- 1989/09/15 00:00 [pubmed]
PHST- 1989/09/15 00:01 [medline]
PHST- 1989/09/15 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1989 Sep 15;49(18):5103-7.