caa a22 4500 477128343 CHVBK 20180405111656.0 cr unu---uuuuu 170330e19970201xx s 000 0 eng 10.1023/A:1012065130597 doi (NATIONALLICENCE)springer-10.1023/A:1012065130597 A Model with Separate Hepato-Portal Compartment ("First-Pass" Model): Fitting to Plasma Concentration-Time Profiles in Humans [Elektronische Daten] [Vladimir Piotrovskij, Achiel Van Peer] Purpose. To demonstrate the value of "first-pass" pharmacokinetic models (FPMs) in which the hepato-portal (HP) system is kinetically separated from the central compartment in fitting pharmacokinetic data obtained after intravenous (IV) and oral administration. Methods. Plasma concentration-time profiles of an investigational drug obtained in six healthy subjects each received 4 mg as an intravenous (IV) bolus dose and 10 mg as an oral solution served as a real data example. The common three- and four-compartment models with the first-order absorption and lag time (3CM and 4CM, respectively) in which HP system is assumed to be part of the central compartment were used as alternative models. We tested also: (i) the sensitivity of the output of FPM to variations in its parameters assuming IV and oral administration; (ii) practical estimability of the FPM parameters by fitting it to 20 simulated noisy data sets; (iii) distinguishability of FPM, 3CM and 4CM by fitting them to the simulated data sets. Results. FPM was shown to give the best fit as compared to 3CM or 4CM in 5 subjects of 6. The sensitivity of FPM was sufficient for the sake of parameter estimation. The "individual" means of parameter estimates obtained after fitting simulated data did not differ significantly from the preselected values. The variance in "individual" estimates was dependent on the sampling frequency. FPM was demonstrated to be distinguishable among relevant models. Conclusions. FPM is preferable as compared to standard compartmen-tal models for drugs extensively taken up by the intestine and/or the liver, and may have a broad spectrum of applications. Plenum Publishing Corporation, 1997 compartmental pharmacokinetic models nationallicence "first pass" effect nationallicence distribution nationallicence liver nationallicence intestine nationallicence sensitivity analysis nationallicence parameter estimability nationallicence NONMEM nationallicence Piotrovskij Vladimir aut Van Peer Achiel aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/2(1997-02-01), 230-237 0724-8741 14:2<230 1997 14 11095 https://doi.org/10.1023/A:1012065130597 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012065130597 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Piotrovskij Vladimir aut NATIONALLICENCE 700 1- Van Peer Achiel aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/2(1997-02-01), 230-237 0724-8741 14:2<230 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer