A limited sampling method for the estimation of vigabatrin maximum plasma concentration and area under the curve.
A limited sampling model (LSM) was developed to estimate the area under the curve (AUC) and maximum plasma concentration (Cmax) for a 1-g oral dose of vigabatrin. The model was developed using the data from 10 healthy subjects and one time point. The following equations describe the model for AUC and Cmax: AUC(predicted) = 5.4 x C3h + 70 and Cmax(predicted) = 0.18 x AUC(0-infinity) + 9.4. The model was validated in 49 subjects who orally received 1-g vigabatrin. This LSM was also used to predict AUC and Cmax volunteers who received 2- and 4-g vigabatrin doses and in renal failure patients who were given a 0.75-g dose. The model provided good estimates of both AUC and Cmax in all groups of subjects except renal dysfunction patients. The method described here may be used to estimate AUC and Cmax of vigabatrin without detailed pharmacokinetic studies.
Tammara
V
V
Division of Pharmaceutical Evaluation I, Food & Drug Administration, Rockville, Maryland 20852, USA.
Mahmood
I
I
Yu
D K
DK
Hileman
G A
GA
D000927:Anticonvulsants / Q000097:blood* / Q000627:therapeutic use; D019540:Area Under Curve; D018592:Cross-Over Studies; D006801:Humans; D051437:Renal Insufficiency / Q000097:blood / Q000188:drug therapy; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use
D000927:Anticonvulsants; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin