N Chamberlin | PubMed Health

PubMed1998

A limited sampling method for the estimation of AUC and Cmax of carbamazepine and carbamazepine epoxide following a single and multiple dose of a sustained-release product.

AIMS: The objectives of this study are to develop a model to predict area under the curve (AUC) and maximum plasma concentration (Cmax) of carbamazepine (CBZ) and its active metabolite carbamazepine epoxide (CBZE) following single and multiple dose of CBZ using one or two samples in volunteers. METHODS: Limited sampling models (LSM) were developed for CBZ and CBZE following 200-800 mg single oral dose and 400-800 mg twice daily dose for 14 days of a sustained-release product (CBZ-SR) to estimate AUC and Cmax. The LSM was developed from a training data set of 15 subjects using one blood sample taken at 48 h following a single dose. The model was validated on 60 subjects who received different doses of CBZ. Following multiple dosing, the LSM was developed from a training data set of 10 subjects using the steady state Cmin (plasma concentration obtained 5 min before the last CBZ-SR dose). RESULTS: The model provided good estimates of AUC and Cmax for CBZ and CBZE. The bias and the precision of the predicted AUC and Cmax for CBZ and CBZE were less than 10% and 15%, respectively. Similar results were obtained when CBZ was given as multiple dose. CONCLUSIONS: The method described here may be used to estimate AUC and Cmax for CBZ and CBZE without detailed pharmacokinetic studies following single or multiple dose of CBZ.

Administration, Oral↗

PubMed1997

A limited sampling approach in bioequivalence studies.

A limited sampling model (LSM) has been developed for an antidepressant immediate-release product (Drug A) and an antiepileptic controlled release product (Drug B) to predict the area under the curve (AUC) and the maximum plasma concentration (Cmax) and to compare the bioequivalence of two formulations of each drug using predicted versus observed AUC and Cmax after a single oral dose. The LSM for drug A was developed using data from 10 healthy people. The correlation between plasma concentration (independent variable) at selected time points with the AUC or Cmax (dependent variable) was evaluated by simple regression analysis. The linear regression that gave the best correlation coefficient (r) for a single sampling time versus AUC or Cmax was chosen as the LSM. The model provided good estimates of AUC and Cmax for drug A. The 90% confidence interval on log transformed observed and predicted AUC and Cmax were as follows: AUC observed = 100% to 118%, AUC predicted = 101% to 117%, Cmax observed = 99% to 125%, and Cmax predicted = 100% to 131%. The LSM for drug B was developed using a similar approach to drug A. The 90% confidence interval on log transformed observed and predicted AUC and Cmax were: AUC observed = 99% to 110%, AUC predicted = 99% to 118%, Cmax observed = 107% to 120%, and Cmax predicted = 99% to 111%. Although the predicted Cmax did not meet the 90% confidence interval for drug A, the method described here may be used to estimate AUC and Cmax for a drug in bioequivalence studies without detailed blood sampling. More research is needed in this direction.

Anticonvulsants↗