Pharmacodynamics and pharmacokinetics of recombinant hirudin via four non-parenteral routes.
One of recombinant hirudin variants, rHV2, a polypeptide used as an anticoagulant agent in clinic, was administered to anesthetized rats via intratracheal, buccal, nasal and rectal routes. Prolongation in clotting time and thrombin time was measured to calculate pharmacological bioavailability. Plasma concentration of rHV2 was determined using a chromogenic thrombin substrate assay and pharmacokinetic parameters were obtained on the basis of a non-compartmental model. Intravenous administration was also performed as the gold standard by which the other routes were compared. Difference in pharmacological bioavailability (P.A.), bioavailability (F) and absorption rate of rHV2 was found for the four non-parenteral routes. The rank order for both P.A. and F was intratracheal>nasal>buccal>rectal. Absorption was more rapid after both intratracheal and rectal administration (tmax approximately 20-40 min), compared with that after nasal and rectal administration. It is evident that the pulmonary route is preferable to other three routes for successful systemic delivery of rHV2.
Liu
Yu
Y
Department of Pharmaceutics, School of Pharmaceutical Science, Peking University Beijing, 38 Xue Yuan Road, Beijing 100083, PR China.
Lu
Wan-liang
WL
Zhang
Xuan
X
Wang
Xue-qing
XQ
Zhang
Hua
H
Zhang
Qiang
Q
D000042:Absorption; D000278:Administration, Buccal; D000281:Administration, Intranasal; D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D006629:Hirudins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013918:Thrombin Time; D013997:Time Factors; D014914:Whole Blood Coagulation Time
D006629:Hirudins; D011994:Recombinant Proteins