Effect of acetazolamide on barbiturate-induced sleeping time in mice. III. Pharmacokinetics of serum elimination and brain distribution.
Effects of acetazolamide (AZA) on the serum elimination and brain distribution of barbital (BA), phenobarbital (PHB), pentobarbital (PEB) and hexobarbital (HB) were studied in mice. When the barbiturates were administered intraperitoneally to mice, the pretreatment of AZA reduced the serum BA and PHB levels, and significantly increased these brain levels. While relatively small and no effects of AZA were observed for the PEB and HB levels, respectively. After the intravenous administration, the serum elimination of these barbiturates were described by the two compartment model. Although the pretreatment of AZA tended to increase the volumes of central compartment and decrease the elimination rate constants for BA, PHB and PEB, the elevated brain levels of the barbiturates could not be explained as the simulated peripheral concentrations. However, it appeared that the prolongation effect of AZA on the BA, PHB and PEB sleeps in mice was associated with the elevated brain barbiturate levels with AZA.
D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D001463:Barbiturates / Q000378:metabolism / Q000494:pharmacology*; D001798:Blood Proteins / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004347:Drug Interactions; D007700:Kinetics; D008297:Male; D051379:Mice; D011485:Protein Binding; D012890:Sleep / Q000187:drug effects; D013997:Time Factors
D001463:Barbiturates; D001798:Blood Proteins; D000086:Acetazolamide