Investigation of the relationship between in vitro and in vivo release behaviors of acamprosate from enteric-coated tablets.
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 mgx2 tablets) of each formulation was orally administered to four beagle dogs under fasting conditions, and the pharmacokinetic parameters were calculated. The mean AUC0-48, Cmax, Tlag and Tmax for the two types of tablets ranged from 41.5-53.6 microg.h/mL, 4.3-4.5 microg/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.
College of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do, 440-746, Korea.
Yun-Seok
YS
Rhee
Seok
S
Park
Tae-Won
TW
Lee
Chun-Woong
CW
Park
Tae-Young
TY
Nam
Tack-Oon
TO
Oh
Ji-Woong
JW
Jeon
Dong-Soo
DS
Lee
Eun-Seok
ES
Park
D000077443:Acamprosate; D000284:Administration, Oral; D000427:Alcohol Deterrents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D002021:Buffers; D002626:Chemistry, Pharmaceutical; D004285:Dogs; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D008297:Male; D010539:Permeability; D015203:Reproducibility of Results; D012995:Solubility; D013608:Tablets, Enteric-Coated; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics
D000427:Alcohol Deterrents; D002021:Buffers; D013608:Tablets, Enteric-Coated; D013654:Taurine; D000077443:Acamprosate