Evaluation of limited sampling models for prediction of oral midazolam AUC for CYP3A phenotyping and drug interaction studies.
Background : The area under the concentration-time curve (AUC) after oral midazolam administration is commonly used for cytochrome P450 (CYP) 3A phenotyping studies. The aim of this investigation was to evaluate a limited sampling strategy for the prediction of AUC with oral midazolam. Methods: A to...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 69; no. 5; pp. 1127 - 1135 |
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| Autores principales: | , |
| Formato: | equations & formulas research tables/charts Journal Article |
| Publicado: |
Springer Nature
May2013
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104281598&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104281598 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: May2013 vid: 69 iid: 5 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 104281598 87390948 10.1007/s00228-012-1437-9 NLM23131857 104281598 ppf: 1127 ppct: 8 formats: fmt: @attributes: type: P tig: atl: Evaluation of limited sampling models for prediction of oral midazolam AUC for CYP3A phenotyping and drug interaction studies. aug: au: Mueller, Silke Drewelow, Bernd affil: Institute of Clinical Pharmacology, University of Rostock, Schillingallee 70 18057 Rostock Germany sug: subj: Midazolam Administration and Dosage Administration, Oral Drug Interactions Evaluation Human ROC Curve Phenotype Step-Wise Multiple Regression Chromatography, Gas Descriptive Statistics Data Analysis Software Models, Statistical Male Female Young Adult Validation Studies Confidence Intervals Male Female ab: Background : The area under the concentration-time curve (AUC) after oral midazolam administration is commonly used for cytochrome P450 (CYP) 3A phenotyping studies. The aim of this investigation was to evaluate a limited sampling strategy for the prediction of AUC with oral midazolam. Methods: A total of 288 concentration-time profiles from 123 healthy volunteers who participated in four previously performed drug interaction studies with intense sampling after a single oral dose of 7.5 mg midazolam were available for evaluation. Of these, 45 profiles served for model building, which was performed by stepwise multiple linear regression, and the remaining 243 datasets served for validation. Mean prediction error (MPE), mean absolute error (MAE) and root mean squared error (RMSE) were calculated to determine bias and precision Results: The one- to four-sampling point models with the best coefficient of correlation were the one-sampling point model (8 h; r = 0.84), the two-sampling point model (0.5 and 8 h; r = 0.93), the three-sampling point model (0.5, 2, and 8 h; r = 0.96), and the four-sampling point model (0.5,1, 2, and 8 h; r = 0.97). However, the one- and two-sampling point models were unable to predict the midazolam AUC due to unacceptable bias and precision. Only the four-sampling point model predicted the very low and very high midazolam AUC of the validation dataset with acceptable precision and bias. The four-sampling point model was also able to predict the geometric mean ratio of the treatment phase over the baseline (with 90 % confidence interval) results of three drug interaction studies in the categories of strong, moderate, and mild induction, as well as no interaction. Conclusion: A four-sampling point limited sampling strategy to predict the oral midazolam AUC for CYP3A phenotyping is proposed. The one-, two- and three-sampling point models were not able to predict midazolam AUC accurately. pubtype: Academic Journal doctype: equations & formulas research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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