Plasma and cerebrospinal fluid concentrations of indomethacin in humans. Relationship to analgesic activity.
Plasma and cerebrospinal fluid (CSF) concentrations of indomethacin have been determined in 52 patients hospitalized for nerve-root compression pain. Samples of blood and CSF were collected at the same time in each subject, 0.5 to 12 h after a single intramuscular injection of 50 mg indomethacin. Analgesic effect was assessed by the absolute and percentage variation in Huskisson's visual analogue scale between dosing and sampling. According to its high lipid solubility, indomethacin rapidly crossed the blood-brain barrier, being detected in CSF 0.5 h after administration. After attainment of equilibrium within 2 h, the CSF level exceeded the free plasma level. Since the drug was extensively bound to serum albumin (99.7 +/- 0.1%), this phenomenon may represent a slight degree of binding of indomethacin in CSF. The analgesic activity was not related to either the plasma or CSF concentration of indomethacin.
Bannwarth
B
B
Laboratoire de Pharmacologie, Faculté de Médecine de Nancy, Vandoeuvre, France.
Netter
P
P
Lapicque
F
F
Péré
P
P
Thomas
P
P
Gaucher
A
A
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000097:blood / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009408:Nerve Compression Syndromes / Q000097:blood / Q000134:cerebrospinal fluid / Q000503:physiopathology*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement
D007213:Indomethacin