Determination of the pharmacokinetics of 2-amino-7-phosphonoheptanoate in rat plasma and cerebrospinal fluid.
The pharmacokinetics of 2-amino-7-phosphonoheptanoate (AP7) in rat plasma and appearance in cerebrospinal fluid (CSF) are reported. Using high-performance liquid chromatography (HPLC) with fluorescence detection, concentrations of AP7 can be detected as low as 1.0 microM. Peak CSF concentrations (12-15 microM) for both the D-AP7 and D,L-AP7 are observed 10-15 min after i.v. administration and amount to approximately 0.1% of a 1 mmol/kg dose. Significant quantities (3 microM) are present in CSF at 2 h and no AP7 is detectable at 4 h. Following i.v. administration, a monoexponential clearance was observed for D-AP7 clearance from plasma, 15.4 +/- 0.8 S.E.M. ml/min/kg with a t1/2 of 38.9 +/- 0.8 S.E.M. min. However, a biexponential clearance from plasma was observed for D,L-AP7.
Compton
R P
RP
Central Nervous System Diseases Research, G.D. Searle & Company, St. Louis, MO 63198.
Hood
W F
WF
Monahan
J B
JB
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003292:Convulsants / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013050:Spectrometry, Fluorescence
D000596:Amino Acids; D003292:Convulsants; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid