Transport of drugs across the Xenopus pulmonary membrane and their absorption enhancement by various absorption enhancers.
OBJECTIVE
The permeability of drugs across the Xenopus pulmonary membrane and the effects of various absorption enhancers on their absorption were examined using an in vitro Ussing chamber technique.


METHODS
Phenol red and fluorescein isothiocyanate-labeled dextrans (FDs) with different molecular weights were chosen as water-soluble model drugs. Absorption enhancers used in this study were N-lauryl-beta-D-maltopyranoside (LM), linoleic acid-HC060 mixed micelle (MM), sodium glycocholate (Na-GC), sodium caprate (Na-Cap), sodium salicylate (Na-Sal) and disodium EDTA (EDTA).


RESULTS
The permeability of drugs gradually decreased with increasing their molecular weights, and the absorption of phenol red significantly increased by these absorption enhancers. Among these additives, LM, MM and Na-Cap appeared to be more effective for enhancing the permeability of drugs than the others. Furthermore, we plotted the logarithm of apparent permeability coefficient (Papp) of these drugs against the logarithm of their molecular weights. There exists a good correlation between these parameters. We measured transmembrane resistance(Rm) of Xenopus pulmonary membrane during the transport experiment to examine the membrane integrity. The average Rm value was about 700 omega.cm2, and this value was maintained for 3 hr.


CONCLUSIONS
This method is useful for estimating the transport characteristics of drugs across the pulmonary membrane.
Okumura
S
S
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
Fukuda
Y
Y
Takahashi
K
K
Fujita
T
T
Yamamoto
A
A
Muranishi
S
S
D000042:Absorption; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003911:Dextrans / Q000737:chemistry / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008970:Molecular Weight; D010637:Phenolsulfonphthalein / Q000737:chemistry / Q000493:pharmacokinetics*; D014982:Xenopus laevis
D003911:Dextrans; D016650:Fluorescein-5-isothiocyanate; D010637:Phenolsulfonphthalein