In-vivo release of a GnRH agonist from a slow-release poly(lactide-glycolide) copolymer preparation: comparison in rat, rabbit and guinea-pig.
Different batches of 50:50 poly((+-)-lactide-glycolide) copolymer (PLG) were used as biodegradable carriers for D-Phe6-gonadotropin-releasing hormone (GnRHa) in the form of injectable long-acting implants loaded with 10% GnRHa and tracer amounts of [125I]GnRHa. After their injection subcutaneously into rats, rabbits, and guinea-pigs, the release kinetics of the peptide were determined by counting the radioactivity remaining in the implants (i) after recovery from the rats after death or (ii) directly on the skin above the injection site of rabbits and guinea-pigs in-vivo. No significant differences in the release pattern of the peptide amongst the three species whether the release process was controlled by diffusion or by degradation of the polymeric matrix were found. It is concluded that the results of in-vivo release tests using laboratory animals are valid for man and that enzymes are not involved in the degradation of the polymeric matrix. The results may be of general importance for the use of long-term release PLG formulations of highly active drugs, especially peptides and proteins.
Institute of Drug Research, Berlin, Germany.
N
N
Heinrich
K
K
Fechner
H
H
Berger
D
D
Lorenz
E
E
Albrecht
G
G
Rafler
H
H
Schäfer
B
B
Mehlis
D000818:Animals; D001673:Biodegradation, Environmental; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007987:Gonadotropin-Releasing Hormone / Q000493:pharmacokinetics*; D006168:Guinea Pigs; D007279:Injections, Subcutaneous; D007457:Iodine Radioisotopes; D019344:Lactic Acid; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000378:metabolism
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007457:Iodine Radioisotopes; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D007987:Gonadotropin-Releasing Hormone; D019344:Lactic Acid