Pharmacokinetic profile of the immunomodulating compound adamantylamide dipeptide (AdDP), a muramyl dipeptide derivative in mice.
A pharmacokinetic profile of 14C-AdDP with uniformly labelled alanine was investigated. It was shown that the distribution phase after an i.v. administration is very short with a half-life of 2.1 min. The half-life of elimination phase after the i.v. administration is about 2.85 hours, that is longer than those of MDP and its derivatives. The total body clearance (30 ml/min/kg) is caused predominantly by metabolism of the compound. All the radioactivity found in urine in a 48 hours interval after a s.c. administration represents only 3.1% of the administered dose. Only a smaller part of the excreted radioactivity is formed by unmetabolised AdDP. The concentration curve after a s.c. administration is characterized by a very fast absorption with a half-life shorter than 1 minute. The distribution and elimination phases are prolonged (20 min, 11 hours respectively) in comparison with an i.v. injection. The decreased absolute bioavailability after a s.c. administration (65%) is probably not biologically significant because of a slower release of the compound from the site of the s.c. administration. A relatively very high radioactivity was found in liver, kidney, thymus, spleen and brain very soon which suggest a very good penetration into tissues. It is an agreement with the high apparent distribution volume of peripheral compartment and higher lipophilicity of AdDP as compared to MDP.
Walder
P
P
Institute of Pharmacology, Czechoslovak Academy of Sciences, Prague.
Buchar
E
E
Machková
Z
Z
Vrba
T
T
Flegel
M
M
Janků
I
I
Masek
K
K
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000493:pharmacokinetics; D000547:Amantadine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000818:Animals; D004151:Dipeptides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D014018:Tissue Distribution
D000276:Adjuvants, Immunologic; D004151:Dipeptides; C044891:adamantylamide-alanyl-isoglutamine; D000547:Amantadine