Excretion of a radiolabelled anticancer biodegradable polymeric implant from the rabbit brain.
The elimination of a clinically used anticancer biodegradable polymer implant (Gliadel) in the rabbit brain was studied. The implant is composed of N,N-bis(2-chloroethyl)-N-nitrosourea (BCNU) (1.6 wt%) dispersed in a copolyanhydride matrix of 1,3-bis(p-carboxyphenoxypropane) (CPP) and sebacic acid (SA) in a 20:80 molar ratio. Four groups of rabbits were implanted with wafers loaded with BCNU, one in a 14C-SA-labelled polymer, another in a 14C-CPP-labelled polymer and two groups with 14C-BCNU in a non-labelled polymer, one for BCNU disposition study and one for residual drug study. In the rabbits implanted with the 14C-SA-labelled polymer, approximately 10% of the radioactivity was found in the urine and 2% in the faeces, and about 10% remained in the device 7 d after implantation. In contrast, only 4% of the radioactivity of the 14C-CPP-labelled polymer was found in urine and faeces during this period. However, a drastic increase in the CPP excretion was found after 9 d, and at 21 d, 64% of the implanted 14C-CPP was found in the urine and faeces, and 29% was still in the recovered wafers. Approximately 50% of the BCNU in the wafers was released in 3 d, and over 95% was released after 6 d in the rabbit brain. This study demonstrates that BCNU-loaded polyanhydride is biodegradable and is excreted from the body primarily through the renal system. The water-soluble components SA and BCNU were rapidly excreted, while the insoluble CPP was gradually eliminated after a lag time of 9 d.
Department of Pharmaceutical Chemistry, School of Pharmacy, Hebrew University of Jerusalem, Israel.
A J
AJ
Domb
M
M
Rock
C
C
Perkin
G
G
Yipchuck
B
B
Broxup
J G
JG
Villemure
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002330:Carmustine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D003652:Decanoic Acids / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine; D003998:Dicarboxylic Acids; D004343:Drug Implants; D062425:Hydroxybenzoate Ethers; D062385:Hydroxybenzoates / Q000493:pharmacokinetics* / Q000652:urine; D011091:Polyesters / Q000737:chemistry; D011817:Rabbits
D018906:Antineoplastic Agents, Alkylating; D002250:Carbon Radioisotopes; D003652:Decanoic Acids; D003998:Dicarboxylic Acids; D004343:Drug Implants; D062425:Hydroxybenzoate Ethers; D062385:Hydroxybenzoates; D011091:Polyesters; C078320:1,3-bis(4-carboxyphenoxy)propane; C055401:decanedioic acid-4,4'-(1,3-propanediylbis(oxy))bis(benzoic acid) copolymer; C011107:sebacic acid; D002330:Carmustine