CONCOMITANT SINGLE-DOSE AND MULTIPLE-DOSE PHARMACOKINETICS OF TERODILINE IN MAN, WITH A NOTE ON ITS ENANTIOMERS AND MAJOR METABOLITES

Citation
B. Hallen et al., CONCOMITANT SINGLE-DOSE AND MULTIPLE-DOSE PHARMACOKINETICS OF TERODILINE IN MAN, WITH A NOTE ON ITS ENANTIOMERS AND MAJOR METABOLITES, Pharmacology & toxicology, 76(3), 1995, pp. 171-177
Citations number
15
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Pharmacy",Toxicology
Journal title
ISSN journal
0901-9928
Volume
76
Issue
3
Year of publication
1995
Pages
171 - 177
Database
ISI
SICI code
0901-9928(1995)76:3<171:CSAMPO>2.0.ZU;2-I
Abstract
Single-dose and multiple-dose pharmacokinetics of terodiline were stud ied in 20 healthy volunteers by giving an initial oral dose of deuteri um-labelled terodiline (12.5 mg or 25 mg) followed by multiple doses o f Mictrol tablets (12.5 mg b.i.d. for 14 days and 25 mg b.i.d. for 14 days or vice versa). The enantiomer serum concentration ratio of S(-)/ R(+) terodiline was close to unity at steady-state as well as during t he disposition phase. The average single-dose kinetic parameters for t he racemate after the 12.5 mg dose were: maximum serum concentration 4 1 mu g/l, the corresponding time 3.4 hr, terminal half-life 61 hr, ora l clearance 77 ml/min., renal clearance 12 ml/min. and apparent Volume of distribution 3821. The single-dose kinetics for the 25 mg dose and the multiple-dose kinetic parameters showed that linear kinetics prev ailed. The average steady-state serum concentration was 275 mu g/l at the lower dose and 509 mu g/l al the higher dose. The degree of fluctu ation during a dosage interval was 19% and the time to steady-stale wa s about 9 days. The fraction unbound was about 8%. Unconjugated p-hydr oxylated terodiline, p-hydroxy-m-methoxyterodiline and hydroxy-tert-bu tyl-terodiline constituted 15%, <1% and 5%, respectively, of the terod iline steady-state levels.