| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2479483 | Drug Metabolism and Pharmacokinetics | 2007 | 9 Pages |
Summary:It is well recognized that the theophylline (TP) concentration in human tears correlates well with the free TP concentration in human plasma. However this correlation was found only in a very narrow range of concentrations of TP, and pharmacokinetic analysis of TP in tears has not been carried out for a wide range of concentrations of TP. The aims of this investigation were to develop a simple kinetic model for TP in guinea pig plasma (total [Cf + b] and free [Cf]), cerebrospinal fluid (CSF) [C]CSF and tears [C]T, and to examine whether [Cf], [Cf + b] and [C]CSF can be predicted from [C]T using the resulting kinetic parameters. [Cf + b], [Cf], [C]CSF and [C]T were determined by GC/EI-SIM following bolus i.v. injection of TP in doses of 10, 50 and 100 mg/kg into guinea pigs. The wide range of concentrations of [Cf + b] could be quantitatively described by a two-compartment model with non-linear elimination kinetics and individual volume distribution of TP at each dose. [C]T and [C]CSF were analyzed using passive diffusion models with and without the pH-partition theory, respectively. The value of [Cf ] could be predicted from the value of [C]T. Thus, the measurement of [C]T which can be collected non-invasively would be a useful method for the therapeutic drug monitoring of TP.
