In vitro hydrolysis of RR,SS-threo-methylphenidate by blood esterases--differential and enantioselective interspecies variability.
Enantioselective in vitro hydrolysis of methylphenidate (MPH) by the blood esterases of seven mammalian species is reported. The species included rats, rabbits, dogs, cattle, horses, monkeys, and humans. In vitro incubations up to 8 h were carried out in plasma, red blood cells, and whole blood of the various species. Enantioselective differences were evident among the different species on comparison of the data obtained from the three biological fluids. The esterases present in plasma appeared to show greater activity in the hydrolysis of MPH in all species where comparison with the other two biofluids was possible. Only in the case of humans did esterases present in plasma and red blood cells demonstrate opposite enantioselectivity in the hydrolysis of MPH. Thus after 8 h incubation, the RR-MPH/SS-MPH ratios in plasma and red blood cells were 0.31 and 1.16, respectively.
Srinivas
N R
NR
College of Pharmacy, University of Saskatchewan, Saskatoon, Canada.
Hubbard
J W
JW
McKay
G
G
Hawes
E M
EM
Midha
K K
KK
D000818:Animals; D002021:Buffers; D002417:Cattle; D002845:Chromatography; D004285:Dogs; D004912:Erythrocytes / Q000201:enzymology; D004950:Esterases / Q000097:blood*; D005260:Female; D006736:Horses; D006801:Humans; D006868:Hydrolysis; D008253:Macaca mulatta; D008297:Male; D008774:Methylphenidate / Q000097:blood*; D010710:Phosphates; D010949:Plasma / Q000201:enzymology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013237:Stereoisomerism
D002021:Buffers; D010710:Phosphates; D008774:Methylphenidate; D004950:Esterases