Effect of parenterally administered atropine on the percutaneous absorption of phencyclidine and methadone

The effect of parenterally administered atropine on the previously demonstrated percutaneous absorption of phencyclidine and methadone was investigated in vivo using the hairless (SKH, hr-1/hr-1) mouse as an experimental model. At both three hours and four hours following topical application of aqueous phencyclidine hydrochloride, the mean drug concentration in liver was significantly lower in mice that had received atropine sulfate by intraperitoneal injection than in mice that had received only water by this route (3 hrs: p less than 0.01; 4 hrs: p less than 0.02). Prior to three hours no statistically significant difference was noted. In contrast, parenteral administration of atropine produced no significant effect upon the percutaneous absorption of aqueous methadone hydrochloride over a four-hour period. Atropine inhibition of absorption is likely due to cutaneous dehydration, and it may be drug-specific and/or dose-related. These findings are correlated with the previously reported ethanol inhibition of percutaneous absorption. The therapeutic implications of these observations are discussed.