title: Pharmacokinetics of theophylline in Guinea pig tears.
abstract: 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.
authors.affiliation: Department of Functional and Analytical Food Sciences, Faculty of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan. sato@nupals.ac.jp
authors.forename: Shinji
authors.initials: S
authors.lastname: Sato
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nakajima
authors.forename: Akira
authors.initials: A
authors.lastname: Honda
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Konishi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyazaki
mesh_terms: D000465:Algorithms; D000628:Aminophylline / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D000818:Animals; D006168:Guinea Pigs; D007276:Injections, Intraventricular; D016018:Least-Squares Analysis; D008297:Male; D008954:Models, Biological; D013666:Tears / Q000737:chemistry / Q000378:metabolism*; D013806:Theophylline / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D014665:Vasodilator Agents; D000628:Aminophylline; D013806:Theophylline