Prediction of plasma concentration-time curve of orally administered theophylline based on a scintigraphic monitoring of gastrointestinal transit in human volunteers.
The plasma concentration-time profile of theophylline after oral administration in human volunteers was predicted using the individual gastrointestinal (GI) transit data monitored by a gamma scintigraphic technique. Theophylline was administered as aminophylline under fasted and fed condition, along with 99mTc-labeled diethylenetriamine-pentaacetic acid (DTPA), an unabsorbable marker to evaluate the GI transit by a gamma scintigraphic technique. Two healthy male volunteers participated under fasted and fed conditions in a crossover study. The GI transit was evaluated by dividing the GI tract to four segments, stomach, jejunum, ileum and cecum/colon. Under the fed condition, the GI transit pattern for each segment was confirmed to alter considerably, causing a delay in the gastric emptying mainly. Further, the plasma concentration curves of theophylline after oral administration were predicted using the GI-Transit-Absorption Model on the basis of individual GI transit parameters calculated by the fitting of the observed data to the GI-Transit Kinetic Model. The absorption rate constant in each segment and the pharmacokinetic parameters after intravenous administration used for the prediction were the values extrapolated from the data in rats and the ones normalized from the values in literatures, respectively. The plasma concentration-time curves for theophylline were well predicted using obtained individual GI transit parameters. The analysis using this method could estimate the variable absorption behavior governed by the GI transit in detail.
Haruta
Shunji
S
Department of Hospital Pharmacy, Miyazaki Medical College, Miyazaki 889-1692, Japan.
Kawai
Keiichi
K
Nishii
Ryuichi
R
Jinnouchi
Seishi
S
Ogawara
Ken ichi
Ki
Higaki
Kazutaka
K
Tamura
Shozo
S
Arimori
Kazuhiko
K
Kimura
Toshikiro
T
D000284:Administration, Oral; D000328:Adult; D001993:Bronchodilator Agents / Q000097:blood; D018592:Cross-Over Studies; D004064:Digestive System / Q000000981:diagnostic imaging* / Q000378:metabolism; D018565:Food-Drug Interactions / Q000502:physiology; D005772:Gastrointestinal Transit / Q000502:physiology*; D006801:Humans; D016014:Linear Models; D008297:Male; D008991:Monitoring, Physiologic / Q000295:instrumentation / Q000379:methods*; D011237:Predictive Value of Tests; D011877:Radionuclide Imaging; D013806:Theophylline / Q000008:administration & dosage* / Q000097:blood*; D013997:Time Factors
D001993:Bronchodilator Agents; D013806:Theophylline