Control of pulmonary absorption of water-soluble compounds by various viscous vehicles.
Effects of various viscous vehicles on the pulmonary absorption of water-soluble drugs were examined by an in situ pulmonary absorption experiment. Gelatin, polyvinylacohol (PVA), hydroxypropylcellose (HPC), chondroitin sulfate A sodium salt (CS), polyacrylic acid (PAA), methylcellulose #400 (MC400) and hyaluronic acid sodium salt (HA) were used as models of viscous vehicles. 5(6)-Carboxyfluorescein (CF) and fluorescein isothiocayanate-labeled dextran with an average molecular weight of 4000 (FD4) were used as water-soluble drugs. The plasma concentration of CF was controlled and regulated in the presence of these viscous vehicles, especially gelatin (1-5%) and polyvinyl alcohol (PVA) 1%. In the pharmacokinetic analysis, the Cmax values of CF significantly decreased, and its Tmax values increased in the presence of these viscous vehicles compared with the control. The MRT and MAT values of CF with these vehicles were significantly higher than those without these vehicles. Therefore, these findings indicated that the viscous vehicles were effective to regulate the absorption rate of CF. On the other hand, the pulmonary absorption of FD4 was not so much affected even in the presence of gelatin and PVA, although PVA slightly decreased MRT value, and significantly decreased Tmax value. Furthermore, we examined the release rate of CF from the cellulose tube containing various concentrations of gelatin. The release rate of CF from the cellulose tube with gelatin was inversely related to the viscosity of gelatin. In addition, the release rate of CF was inversely related to DeltaMAT (DeltaMAT = MATgel(MAT with gelatin)-MATsol(MAT without gelatin)) in the presence of varying concentrations of gelatin. These findings indicated that these viscous vehicles were effective to control the pulmonary absorption of CF, a water-soluble drug with low molecular weight and they might be useful to increase the local concentration of drugs in the lung.
Yamamoto
Akira
A
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan. yamamoto@mb.kyoto-phu.ac.jp
Yamada
Keigo
K
Muramatsu
Hideaki
H
Nishinaka
Asako
A
Okumura
Shigeki
S
Okada
Naoki
N
Fujita
Takuya
T
Muranishi
Shozo
S
D000042:Absorption; D000818:Animals; D019540:Area Under Curve; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D019793:Fluorescein; D005452:Fluoresceins / Q000493:pharmacokinetics; D017879:Isothiocyanates / Q000493:pharmacokinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D019999:Pharmaceutical Solutions; D014677:Pharmaceutical Vehicles; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D014783:Viscosity; D014867:Water
D005452:Fluoresceins; D017879:Isothiocyanates; D019999:Pharmaceutical Solutions; D014677:Pharmaceutical Vehicles; D014867:Water; C037152:isothiocyanic acid; C024098:6-carboxyfluorescein; D019793:Fluorescein