Acamprosate calcium is a highly soluble drug with low permeability that is used to maintain abstinence in alcohol-dependent patients. The aim of this study was to investigate the relationship between in vitro and in vivo behaviors of acamprosate from enteric-coated tablets. The in vitro release behavior of acamprosate tablets in pH 6.8 buffer solution was determined in three dissolution conditions, 50 and 150 rpm (paddle method) and 180 rpm (basket method). The results of this in vitro experiment indicated that acamprosate tablets hardly disintegrated, and drug dissolution was retarded despite the extremely hydrophilic nature of the drug. A single dose ($333;mg{ imes}2$ tablets) of each formulation was orally administered to four beagle dogs under fasting conditions, and the pharmacokinetic parameters were calculated. The mean $AUC_{0-48}$, $C_{max}$, $T_{lag}$ and $T_{max}$ for the two types of tablets ranged from $41.5-53.6;{mu}g{cdot}h/mL$, $4.3-4.5;{mu}g/mL$, 2.0-2.5 h and 3.8-4.0 h, respectively. In conclusion, it is suggested that retarded drug release from the tablets and the low drug permeability may result in poor absorption and erratic bioavailability of this drug in humans.