title: In vivo evaluation of the semi-simultaneous method for bioavailability estimation using controlled intravenous infusion as an 'extravascular' route of administration.
abstract: A recently proposed method for bioavailability estimation, called the semi-simultaneous method, was evaluated in vivo in rats using methysergide as a test substance. In this method the test and the reference dose are administered with a short time interval and a model including the bioavailability parameters is fitted to the concentration-time profile. In the present study, in order to control the true bioavailability, intravenous infusion was used to mimic extravascular administration and various input profiles were produced. Mono-, bi- and triexponential disposition functions with the true and also various erroneous input models were fitted to the individual data sets. The models were also fitted to truncated data sets to mimic a situation where a long duration of sampling is precluded. A combined fitting-deconvolution procedure was also applied. The simi-simultaneous method gave precise and accurate estimates of the bioavailability in most groups and a robustness in the estimate concerning the model fitted was noted. The true input model could be identified for all data sets using common goodness-of-fit criteria. In the groups where a 'flip-flop' situation was created (slower input than elimination) a poorer precision and accuracy and a higher sensitivity concerning the model fitted was observed. The model fitting and the fitting-deconvolution procedure generally gave very similar results.
authors.affiliation: Department of Biopharmaceutics and Pharmacokinetics, University of Uppsala, Sweden.
authors.forename: U
authors.initials: U
authors.lastname: Bredberg
authors.forename: M O
authors.initials: MO
authors.lastname: Karlsson
mesh_terms: D000818:Animals; D001682:Biological Availability; D005069:Evaluation Studies as Topic; D007262:Infusions, Intravenous; D008297:Male; D008722:Methods; D008784:Methysergide / Q000493:pharmacokinetics; D010599:Pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D008784:Methysergide