Pharmacokinetics do not explain the absence of an anesthetic effect of perfluoropropane or perfluoropentane.
In conflict with the prediction of the Meyer-Overton hypothesis, perfluoropropane (C3F8) and perfluoropentane (C5F12) have no anesthetic effect in rats. To test whether this resulted from a failure of the inspired drugs to reach the brain, we determined the increase in partial pressures of C3F8 and C5F12 in the blood and brains of rats exposed to 0.65 ata of each drug. C3F8 and C5F12 blood/gas partition coefficients equaled 0.00125 +/- 0.00037 (mean +/- SD, n = 9) and 0.00277 +/- 0.00082 (n = 4), and brain/gas partition coefficients equaled 0.0119 +/- 0.0002 (n = 4) and 0.0229 +/- 0.0055 (n = 7), respectively. As a fraction of the inspired value (Pa/PI), the partial pressures of C3F8 and C5F12 in blood (Pa) were 0.99 +/- 0.12 and 0.69 +/- 0.19, respectively, 30 min after administration. The increases in cerebral (Pb) partial pressures of both drugs paralleled the arterial increases (Pb/PI = 0.85 +/- 0.02, and 1.05 +/- 0.03, respectively at 30 min), with C3F8 reaching a plateau at 2 h of 96% +/- 4% of the partial pressure of inspired gas. We conclude that failure of C3F8 and C5F12 to reach the brain does not account for the absence of an anesthetic effect of these compounds.
Chortkoff
B S
BS
Department of Anesthesia, University of California, San Francisco 94143-0648, USA.
Laster
M J
MJ
Koblin
D D
DD
Taheri
S
S
Eger
E I
EI
Halsey
M J
MJ
D000769:Anesthesia, Inhalation; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D005466:Fluorocarbons / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D010420:Pentanes
D005466:Fluorocarbons; C008806:perfluoropentane; D010420:Pentanes; C042852:perflutren