Pharmacokinetic profile of the immunomodulating compound adamantylamide dipeptide (AdDP), a muramyl dipeptide derivative in mice

Immunopharmacol Immunotoxicol. 1991;13(1-2):101-19. doi: 10.3109/08923979109019694.

Abstract

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.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / pharmacokinetics
  • Amantadine / administration & dosage
  • Amantadine / analogs & derivatives*
  • Amantadine / pharmacokinetics
  • Animals
  • Dipeptides / administration & dosage
  • Dipeptides / pharmacokinetics*
  • Half-Life
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Male
  • Metabolic Clearance Rate
  • Mice
  • Tissue Distribution

Substances

  • Adjuvants, Immunologic
  • Dipeptides
  • adamantylamide-alanyl-isoglutamine
  • Amantadine