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Effect of several enhancers on the skin permeation of water-soluble drugs.

Since the percutaneous absorption rates of water-soluble drugs are low in general, an enhancing system is needed when using the skin as an administration site for the drugs. We have investigated the effect of various penetration enhancers on the in vitro and in vivo percutaneous absorptions of catecholamine analogs, i.e. levodopa (LD), dopamine hydrochloride (DPH) and isoproterenol hydrochloride (IPH), as model water-soluble drugs. It was found that medium-chain glycerides (Sefsol 318) markedly enhanced the in vitro permeation of the drugs through excised hairless rat skin among the enhancers tested in the present experiments; the permeation rates with 5% Sefsol 318 in water were about 65, 34 and 53 times higher than the corresponding control (without enhancer) for LD, DPH and IPH, respectively. In addition, the in vivo percutaneous absorption experiments showed that the blood levels of these drugs after application of aqueous gels containing 5% Sefsol 318 on rat skin were higher than those in the absence of enhancer. Drug levels in the liver and kidney were also higher than without Sefsol 318. Percutaneous administration of DPH with Sefsol 318 to hairless rats resulted in lower diastolic blood pressure and a slightly higher heart rate with as compared to administration without the enhancer. These results suggest that Sefsol 318 is a potential candidate to enhance the transdermal absorption of water-soluble drugs.