Pharmacokinetic difference between S-(+)- and R-(-)-etodolac in rats.
OBJECTIVE
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(lambdaz) 18+/-4 h vs 19.4+/-2.2 h, tmax 3.3+/-2.6 h vs 4+/-4 h; Cmax 29+/-6 mg/L vs 97+/-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(lambdaz), 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 S-etolodac (P<0.05).


CONCLUSIONS
There is pharmacokinetic difference between S-(+)- and R-(-)- etodolac enantiomers in rats after oral administration.
Shi
Jing-Min
JM
Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.
Lai
Shun-Guo
SG
Xu
Chang-Jiang
CJ
Duan
Geng-Li
GL
Li
Duan
D
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D017308:Etodolac / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017308:Etodolac