Saliva-catalyzed hydrolysis of a ketobemidone ester prodrug: Factors influencing human salivary esterase activity

TY - JOUR

T1 - Saliva-catalyzed hydrolysis of a ketobemidone ester prodrug

T2 - Factors influencing human salivary esterase activity

AU - Hansen, L.B.

AU - Christrup, Lona Louring

AU - Bundgaard, H.

PY - 1992/1/1

Y1 - 1992/1/1

N2 - Saliva enzyme-catalysed hydrolysis of ester prodrugs or drugs containing sensitive ester groups may be a limiting factor for the buccal absorption of such compounds. Using the isopropyl carbonate ester of ketobemidone as a model substance of a hydrolysis-sensitive prodrug the esterase activity of human saliva has been characterized as a function of various factors. The esterase activity was found to decrease rapidly upon storage of the saliva at 37°C. The activity increased with increasing pH in the range 4.5-7.4 and with increasing salivation flow rate up to a rate of 0.9 ml min. Under resting conditions, the flow rate was about 0.2 ml min which implied a greatly decreased esterase activity. The activity was highest after fasting and decreased after intake of a meal. The intraindividual variation in the saliva esterase activity was small whereas a larger interindividual variation was found.

AB - Saliva enzyme-catalysed hydrolysis of ester prodrugs or drugs containing sensitive ester groups may be a limiting factor for the buccal absorption of such compounds. Using the isopropyl carbonate ester of ketobemidone as a model substance of a hydrolysis-sensitive prodrug the esterase activity of human saliva has been characterized as a function of various factors. The esterase activity was found to decrease rapidly upon storage of the saliva at 37°C. The activity increased with increasing pH in the range 4.5-7.4 and with increasing salivation flow rate up to a rate of 0.9 ml min. Under resting conditions, the flow rate was about 0.2 ml min which implied a greatly decreased esterase activity. The activity was highest after fasting and decreased after intake of a meal. The intraindividual variation in the saliva esterase activity was small whereas a larger interindividual variation was found.

UR - http://www.scopus.com/inward/record.url?scp=0026727250&partnerID=8YFLogxK

U2 - 10.1016/0378-5173(92)90319-W

DO - 10.1016/0378-5173(92)90319-W

M3 - Journal article

AN - SCOPUS:0026727250

SN - 0378-5173

VL - 88

SP - 221

EP - 227

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

IS - 1-3

ER -