Dustri Online Services

Search Results

Books: 0	Journals: 1	Articles: 1

Original

Limitations of fexofenadine limited sampling strategy using plasma concentrations and partial area under the concentration-time curve to estimate transporter activity in healthy adults 

Marlon Liyanage, Chelsea L. Blaquera, Joseph Piscitelli, Scott R. Penzak, Thomas D. Nolin, Mary F. Paine, and Joseph D. Ma

Price
42.00 $

Price

42.00 $

Add to Cart ###ENGLISH_ABSTRACT_LINK### ###FREE_ENGLISH_ARTICLE_DOWNLIAD_LINK###

Volume 61 (2023) p. 262 - 269

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 61 – No. 6/2023 (262-269)

Limitations of fexofenadine limited sampling strategy using plasma concentrations and partial area under the concentration-time curve to estimate transporter activity in healthy adults 

Marlon Liyanage¹, Chelsea L. Blaquera¹, Joseph Piscitelli¹, Scott R. Penzak², Thomas D. Nolin³, Mary F. Paine⁴, Joseph D. Ma¹ 

¹Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, ²Harrison School of Pharmacy, Auburn University, Auburn, AL, ³University of Pittsburgh School of Pharmacy, Pittsburgh, PA, and ⁴College of Pharmacy & Pharmaceutical Sciences, Washington State University, Spokane, WA, USA
Objective: Fexofenadine is a probe drug used to phenotype P-glycoprotein (P-gp) and organic anion transporting polypeptide (OATP) 1B1/3 activities. This study evaluated a limited sampling strategy using plasma concentrations and/or partial area under the concentration versus time curves (AUCs) to estimate systemic exposure and, potentially, P-gp and OATP1B1/3 activities.
Materials and methods: Plasma concentration versus time data were obtained from 53 healthy adult participants (22 females) from four published studies. Participants were administered a single oral dose (120 mg) of fexofenadine during constitutive P-gp and OATP1B1/3 conditions. Concentration-time data were divided into a training (n = 18) and validation (n = 35) set. Backwards stepwise linear regression generated single-, 2-timepoint, and partial AUC limited sampling models (LSMs). Noncompartmental analysis methods were used to determine total AUC (AUC_0–lNF) from intensive sampling. Coefficient of determination (r²) and bias and precision were assessed via relative percent mean prediction error (%MPE), relative percent mean absolute error (%MAE), and relative percent root mean square error (%RMSE).
Results: The geometric mean observed AUC_0–INF was 1,680 ng×h/mL. The 2-, 5-, and 2- plus 5-hour LSMs met backwards stepwise linear regression significance (p < 0.15) to remain in the model but had unacceptable %RMSE (17 – 29%). The majority of partial AUC LSMs had unacceptable r² (0.21 – 0.83), with all models having unacceptable %MAE (12 – 35%).
Conclusion: Fexofenadine limited sampling strategy using single-timepoint, 2-timepoint, and partial AUCs were unable to accurately estimate AUC_0–lNF and thus constitutive P-gp and OATB1B1/3 activities in healthy adults. Timepoints that were not measured or selected may have improved LSM performance.Correspondence to:
Joseph D. Ma, PharmD
University of California, San Diego
Skaggs School of Pharmacy and Pharmaceutical Sciences
9500 Gilman Drive, MC 0657
La Jolla, CA 92093-0657, USA
Email: [email protected]

Warenkorb Übersicht

Warenkorb Übersicht
Typ	Anz	Rabatt	MwSt	Preis
Der Warenkorb ist leer

Ihr Warenkorb

Search Results

Warenkorb Übersicht

Senden Sie uns eine E-Mail