Effects of viscous hyaluronate-sodium solutions on the nasal absorption of vasopressin and an analogue.
The effects of viscous solutions of hyaluronate-sodium of various average molecular weights (MW) on the nasal absorption of vasopressin (AVP) and its analogue, 1-deamino-8-D-arginine vasopressin (1-d-8-DAVP), were examined in rats. Solutions of hyaluronate with MW greater than 3 x 10(5) daltons enhanced the nasal absorption of AVP; solutions of MW 5.5 x 10(4) daltons were not effective. The enhancing effects on the nasal absorption of AVP and 1-d-8-DAVP were dependent on the concentration in the range of 0-1.5% (w/v) hyaluronate (MW 1.4 x 10(6) daltons). The nasal absorption of AVP was increased with this solution at lower pH. Bioavailabilities after nasal administration of AVP and 1-d-8-DAVP in hyaluronate solutions (MW 1.4 x 10(6) and 2 x 10(6) daltons) increased more than 2-and 1.6-fold as compared to nasal administration of AVP and 1-d-8-DAVP in buffer solutions (pH 7.0), respectively. Hyaluronate solution (MW 1.4 x 10(6) daltons) did not affect the ciliary beat frequency of rabbit nasal mucosal membranes in vitro. Therefore, hyaluronate solution may be useful as a vehicle for nasal delivery of AVP and 1-d-8-DAVP.
Morimoto
K
K
Department of Pharmaceutical Sciences, Osaka University of Pharmaceutical Sciences, Japan.
Yamaguchi
H
H
Iwakura
Y
Y
Morisaka
K
K
Ohashi
Y
Y
Nakai
Y
Y
D000042:Absorption / Q000187:drug effects; D000268:Adhesiveness; D000281:Administration, Intranasal; D000818:Animals; D001682:Biological Availability; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009079:Mucociliary Clearance / Q000187:drug effects; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012996:Solutions; D014667:Vasopressins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014783:Viscosity
D012996:Solutions; D014667:Vasopressins; D006820:Hyaluronic Acid; D003894:Deamino Arginine Vasopressin