[Kinetics of immunoglobulin G transport through the multi-layer epithelial-hematic barrier of the respiratory tract].
A new class of drugs is now utilized for in vivo diagnoses and therapy of many widespread diseases. In these pharmacological and diagnostic preparations the active substance is conjugated with a vector which transports the drug to specific biological targets. Monoclonal antibodies are the most commonly used vectors: estimation of their permeability through multilayer and unilayer biomembranes is an important step in the analysis of efficiency of vector drugs. Experiments with Sprague-Dawley rats (mature females weighing 500 to 160 g) have demonstrated the ability of immunoglobulins G to penetrate through the respiratory epithelial-hematic barrier. Using solid phase ELISA, it was found that 5-25% of the total amount of mouse antiinsulin immunoglobulins G1 injected into the trachea under hexenal anesthesia can penetrate into the blood plasma. Accumulation of antibodies in the blood begins 4 hours and ceases 32 hours after the drug application in a dose of 400 micrograms. The kinetics of transmembrane transport is described by an S-like saturation function: C(t) = Cmax/(1+e-(at-b]. Penetration of monoclonal antibodies into the blood is accompanied by their distribution in the organs and tissues as well as by their clearance from the blood plasma. The clearance of monoclonal antibodies is characterized by a 24 hour half-life and is described by an exponential equation: C(t) = C0 x exp-kt. An algorithm for the interaction of these processes which should be taken into account during measurements of the transport of monoclonal antibodies and their complexes through biomembranes is proposed.(ABSTRACT TRUNCATED AT 250 WORDS)
Ermakov
N V
NV
Krekhnov
B V
BV
Chenchikova
E Iu
EIu
Cherchenko
N G
NG
Ishkov
A G
AG
Remizova
E N
EN
Sveshnikov
P G
PG
Miroshnichenko
E V
EV
Nazarov
Iu V
IuV
Morozov
A P
AP
D000818:Animals; D000911:Antibodies, Monoclonal; D001692:Biological Transport; D001808:Blood Vessels / Q000378:metabolism*; D002199:Capillary Permeability; D004848:Epithelium / Q000378:metabolism*; D005260:Female; D007074:Immunoglobulin G / Q000378:metabolism*; D007700:Kinetics; D051381:Rats; D011919:Rats, Inbred Strains; D014132:Trachea / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G
Kinetika transporta immunoglobulina G cherez mnogosloĭnyĭ épitelial'no-gematicheskiĭ bar'er dykhatel'nykh puteĭ.