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Pharmacokinetics and Saturable Absorption of Gabapentin in Nursing Home Elderly Patients

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Abstract

Pharmacokinetic data of gabapentin (GBP) in community-dwelling elderly patients show a significant effect of advanced age on GBP pharmacokinetics due to altered renal function. However, there are no data in elderly nursing home (NH) patients to evaluate gabapentin absorption and elimination. Our objective was to characterize the pharmacokinetics of GBP in elderly nursing home patients maintained on GBP therapy. This was a prospective pharmacokinetic study in elderly nursing home patients (≥60 years) receiving GBP for the management of chronic pain or epilepsy from seven nursing homes. Pharmacokinetic parameters were estimated by nonlinear mixed-effects modeling. A one-compartment model described the data and clearance (CL) was associated with estimated glomerular filtration rate (eGFR) (p < 0.0001). The GBP CL in elderly nursing home patients was 2.93 L/h. After adjusting for the effect of GFR, GBP CL was not affected by age, sex, body weight, or comorbidity scores. No significant effects of body size measures, age, and sex were detected on volume of distribution. Dose-dependent bioavailability of GBP was demonstrated, and the saturable absorption profile was described by a nonlinear hyperbolic function. Prediction-corrected visual predictive check (pc-VPC) suggests adequate fixed- and random-effects models that successfully simulated the mean trend and variability in gabapentin concentration-time profiles. In this analysis, the parameters of the hyperbolic nonlinearity appear to be similar between elderly and younger adults.

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Acknowledgements

This project was supported by the National Institute on Aging of the National Institutes of Health R01AG026390. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Room 463, 717 Delaware St., SE, Minneapolis, Minnesota, 55414, USA

    Ghada F. Ahmed, Sai Praneeth R. Bathena, Richard C. Brundage, Ilo E. Leppik, Jeannine M. Conway & Angela K. Birnbaum

  2. Center for Clinical and Cognitive Neuropharmacology, University of Minnesota, Minneapolis, Minnesota, USA

    Ilo E. Leppik & Angela K. Birnbaum

  3. Department of Neurology, University of Minnesota, Minneapolis, Minnesota, USA

    Ilo E. Leppik

  4. Departments of Medicine and Bioengineering and Therapeutic Sciences, University of California, San Francisco and Jewish Home of San Francisco, San Francisco, California, USA

    Janice B. Schwartz

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  1. Ghada F. Ahmed
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  2. Sai Praneeth R. Bathena
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Correspondence to Angela K. Birnbaum.

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Ahmed, G.F., Bathena, S.P.R., Brundage, R.C. et al. Pharmacokinetics and Saturable Absorption of Gabapentin in Nursing Home Elderly Patients. AAPS J 19, 551–556 (2017). https://doi.org/10.1208/s12248-016-0022-z

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  • DOI: https://doi.org/10.1208/s12248-016-0022-z

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