Evaluation of Omeprazole Limited Sampling Strategies to Estimate Constitutive Cytochrome P450 2C19 Activity in Healthy Adults

Lin, Swan; Nikanjam, Mina; Capparelli, Edmund V.; Allegrini, Alessandro; Pavone, Daniele; Hammami, Muhammad M.; Bertino, Joseph S.; Nafziger, Anne N.; Park, Yoo-Sin; Kang, Ju‐Seop; Yin, Ophelia; Joseph, D.

doi:10.1097/ftd.0000000000000554

Cited by 2 publications

(3 citation statements)

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“…17 By contrast, LSMs using a population pharmacokinetic approach were unable to accurately estimate CYP2C19 activity using omeprazole as the probe drug. 16 The 1, 2, and 2-plus 8-h LSMs showed unacceptable R 2 values and/or exceeded the acceptable limits of bias and precision. One confounding factor was the influence of distribution at early time points, affecting LSMs at 1 and/or 2 hours.…”

Section: Discussionmentioning

confidence: 87%

“…17 By contrast, LSMs using a population pharmacokinetic approach were unable to accurately estimate CYP2C19 activity using omeprazole as the probe drug. 16…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12][13][14][15] A limited sampling strategy involving a population pharmacokinetic approach has been evaluated to estimate CYP2C9, CYP2C19, and CYP3A activities with various probe drugs. [16][17][18] An advantage of such an approach is flexibility in plasma collection times. A traditional limited sampling strategy using noncompartmental analysis does not allow for deviations in sample collection time points.…”

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confidence: 99%

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Fexofenadine Plasma Concentrations to Estimate Systemic Exposure in Healthy Adults Using a Limited Sampling Strategy with a Population Pharmacokinetic Approach

Piscitelli

Nikanjam

Capparelli

et al. 2023

Therapeutic Drug Monitoring

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Background: Fexofenadine is a recommended in vivo probe drug for phenotyping P-glycoprotein (P-gp) and organic anion transporting polypeptide (OATP) 1B1/3 transporter activities. This study evaluated a limited sampling strategy using a population pharmacokinetic approach to estimate plasma fexofenadine exposure as an index of P-gp and OATP activities.Methods: In a previous study, a single oral dose of fexofenadine (120 mg) was administered alone or in combination with grapefruit juice, Panax ginseng, or Echinacea purpurea to healthy adult participants. Serial plasma samples were collected up to 72 hours after administration and fexofenadine concentrations were measured. A population pharmacokinetic model was developed using nonlinear mixed-effects modeling. Limited sampling models (LSMs) using single and 2timepoint fexofenadine concentrations were compared with full profiles from intense sampling using empirical Bayesian post hoc estimations of systemic exposure derived from the population pharmacokinetic model. Predefined criteria for LSM selection and validation included a coefficient of determination (R 2 ) $ 0.90, relative percent mean prediction error $ 25 to #5%, relative percent mean absolute error # 10%, and relative percent root mean square error # 15%.Results: Fexofenadine concentrations (n = 1520) were well described using a 2-compartment model. Grapefruit juice decreased the relative oral bioavailability of fexofenadine by 25%, whereas P. ginseng and E. purpurea had no effect. All the evaluated single timepoint fexofenadine LSMs showed unacceptable percent mean prediction error, percent mean absolute error, and/or percent root mean square error. Although adding a second time point improved precision, the predefined criteria were not met.Conclusions: Identifying novel fexofenadine LSMs to estimate P-gp and OATP1B1/3 activities in healthy adults for future transporter-mediated drug-drug interaction studies remains elusive.

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Section: Discussionmentioning

confidence: 87%

“…17 By contrast, LSMs using a population pharmacokinetic approach were unable to accurately estimate CYP2C19 activity using omeprazole as the probe drug. 16…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Fexofenadine Plasma Concentrations to Estimate Systemic Exposure in Healthy Adults Using a Limited Sampling Strategy with a Population Pharmacokinetic Approach

Piscitelli

Nikanjam

Capparelli

et al. 2023

Therapeutic Drug Monitoring

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