title: [Pharmacokinetic basis of mannitol administration in the treatment of raised ICP].
abstract: To study the most effective way of mannitol administration for the treatment of raised intracranial pressure (ICP), pharmacokinetics of mannitol were analysed, and the relationship among mannitol concentration, serum osmolality and changes of intracranial pressure (ICP) were examined in cats. 10%, 20% and 30% of mannitol were made and intravenously administrated with the same volume and speed (0.667 ml/kg/min) for 15 minutes to each mannitol concentration group of cats. Sequential changes of ICP were monitored and serial mannitol concentration, serum osmolality and electrolytes were then performed. Changes of mannitol concentration showed a biexponential curve and best fitted to the two-compartment model analysis. There was a strong positive correlation (r = 0.9286) between mannitol concentration and extrinsic serum osmolality. The disposition of mannitol in cats was similar to that which had been reported in dogs and humans. The distribution half-time was faster in 30% mannitol, but the elimination half-time was similar in all groups. The integrated values of mannitol concentration difference between the central (Cc) and the peripheral compartment (Pc) were greatly correlated with the changes of ICP reduction during mannitol administration (for 15min). The time to vanish the mannitol concentration difference between Cc and Pc showed strong reverse correlation with the time to reach the lowest ICP level. The result indicates that the more rapidly mannitol was administrated, the more rapidly the concentration difference between the two compartments was created, and, the higher the effective osmolality was developed, then, the more profound and prolonged ICP reduction can be obtained.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: School of Pharmaceutical Sciences, Kitasato University.
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshiyama
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: F
authors.initials: F
authors.lastname: Tomonaga
authors.forename: R
authors.initials: R
authors.lastname: Kondo
authors.forename: H
authors.initials: H
authors.lastname: Takagi
authors.forename: T
authors.initials: T
authors.lastname: Ohwada
mesh_terms: D000818:Animals; D002415:Cats; D007427:Intracranial Pressure / Q000187:drug effects*; D008353:Mannitol / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009994:Osmolar Concentration; D011559:Pseudotumor Cerebri / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D008353:Mannitol