Pharmacokinetic difference between S-(+)- and R-(-)-etodolac in rats  

作　　者：Jing-minSHI Shun-guoLAI Chang-jiangXU Geng-liDUAN DuanLI 

机构地区：[2]ShanghaiInstituteforDrugControl [3]DepartmentofPharmacologySchoolofPharmacy,FudanUniversity,Shanghai200032,China [4]DepartmentofPharmaceuticalAnalysis,SchoolofPharmacy,FudanUniversity,Shanghai200032,China

出　　处：《Acta Pharmacologica Sinica》2004年第8期996-999,共4页中国药理学报（英文版）

摘　　要：AIM: To study whether etodolac enantiomers have pharmacokinetic difference after oral administration. METHODS: Fourteen rats, divided into two groups randomly, were orally given S-(+)- or R-(-)-etodolac at a single dose of 20 mg/kg, respectively. Blood samples were collected before and at 5, 10, 20, 30 min and 1, 3, 6, 12, 24, 48, 72 h after treatment. The plasma samples were analyzed with a high-performance liquid chromatographic method. RESULTS: The calibration curves were linear in the range of 0.5-50.0 mg/L (r=0.9999) to S-(+)-etodolac and 2.0-200.0 mg/L (r=0.9999) to R-(-)-etodolac, respectively. The main pharmacokinetic parameters of S-(+)- and R-(-)-etodolac were as follows: t1/2(λz)18±4 h vs 19.4±2.2 h, tmax 3.3±2.6 h vs 4±4 h; Cmax 29±6 mg/L vs97±14 mg/L, AUC0-t 706±100 h·mg·L-1 vs 2940±400 h·mg·L-1, CL(s) 0.030±0.006 L·kg-1·h-1 vs 0.0065±0.0010 L·kg-1·h-1 and V/F 0.25±0.22 L·kg-1 vs 0.03±0.05 L·kg-1. There was no significant difference in t1/2(λz) and tmax between S-(+)- and R-(-)-etodolac (P>0.05). The Cmax, and AUC0-t of R-(-)-etodolac were markedly higher (P<0.05), while the CL(s) and V/F were markedly lower than those of 5-etolodac (P<0.05). CONCLUSION: There is pharmacokinetic difference between S-(+)- and R-(-)- etodolac enantiomers in rats after oral administration.AIM: To study whether etodolac enantiomers have pharmacokinetic difference after oral administration. METHODS: Fourteen rats, divided into two groups randomly, were orally given S-(+)- or R-(-)-etodolac at a single dose of 20 mg/kg, respectively. Blood samples were collected before and at 5, 10, 20, 30 min and 1, 3, 6, 12, 24, 48, 72 h after treatment. The plasma samples were analyzed with a high-performance liquid chromatographic method. RESULTS: The calibration curves were linear in the range of 0.5-50.0 mg/L (r=0.9999) to S-(+)-etodolac and 2.0-200.0 mg/L (r=0.9999) to R-(-)-etodolac, respectively. The main pharmacokinetic parameters of S-(+)- and R-(-)-etodolac were as follows: t1/2(λz)18±4 h vs 19.4±2.2 h, tmax 3.3±2.6 h vs 4±4 h; Cmax 29±6 mg/L vs97±14 mg/L, AUC0-t 706±100 h·mg·L-1 vs 2940±400 h·mg·L-1, CL(s) 0.030±0.006 L·kg-1·h-1 vs 0.0065±0.0010 L·kg-1·h-1 and V/F 0.25±0.22 L·kg-1 vs 0.03±0.05 L·kg-1. There was no significant difference in t1/2(λz) and tmax between S-(+)- and R-(-)-etodolac (P>0.05). The Cmax, and AUC0-t of R-(-)-etodolac were markedly higher (P<0.05), while the CL(s) and V/F were markedly lower than those of 5-etolodac (P<0.05). CONCLUSION: There is pharmacokinetic difference between S-(+)- and R-(-)- etodolac enantiomers in rats after oral administration.

关 键 词：ETODOLAC non-steroidal anti-inflammatory agents PHARMACOKINETICS STEREOISOMERISM 

分 类 号：R971.1[医药卫生—药品]