title: Pharmacodynamics and pharmacokinetics of recombinant hirudin via four non-parenteral routes.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Science, Peking University Beijing, 38 Xue Yuan Road, Beijing 100083, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Wan-liang
authors.initials: WL
authors.lastname: Lu
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Xue-qing
authors.initials: XQ
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: 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
chemical_list: D006629:Hirudins; D011994:Recombinant Proteins