Abstracts

Rationale: Rationale: Iron supplementation may affect the levels of many medicines (1), but an effect of iron on carbamazepine (CBZ) has not been previously reported. Persons in nursing homes receive a number of medications including iron supplementation that may interfere with the pharmacokinetics of carbamazepine (CBZ). Methods: Methods: Inclusion criteria were residency in a nursing home for at least 2 months, age 65 years or older, a stable dosing regimen of CBZ for at least 4 weeks (considered steady state), available CBZ concentration, and complete dosing information. CBZ concentration data collected retrospectively from 60 nursing homes across the US were evaluated. The data collected included date, locations of nursing homes, sex, height, weight, date and time of blood draw, total serum concentration, usual dosing frequency, the date, time and dose of the four most recent administrations of CBZ, length of time on current dosing regimen, and co-medications received up to 7 days prior to the serum concentration. The population PK analysis was performed using a nonlinear mixed effects model (NONMEM Version 7.3, ICON Development Solutions, Hanover, MD, U.S.A.). The influence of these fixed effects was evaluated with the objective function value (OFV) and the distribution of the weighted residuals. Model evaluation was performed using a nonparametric bootstrap and prediction-corrected visual predictive check. Results: Results: The final data set consisted of 345 CBZ concentrations from 99 subjects (38 males, 61 females). The population estimate of apparent clearance (CL/F) for a 70-kg person was 3.69 L/hr (RSE 6.9 %). Residents were receiving both immediate (93.9 %) and extended release (6.1 %) formulations and the Ka of each formulation was fixed to literature values. Age, sex, and co-medications had no effect on CL/F and apparent volume of distribution. Iron supplementation which was taken by 16% of the residents resulted in a 33% decrease in bioavailability (?OFV=25.7, p < 0.001). Conclusions: Conclusions: Although iron supplementation exhibited an effect on CBZ CL/F, it is more plausible that iron may inhibit absorption of CBZ in the gastrointestinal tract resulting in an increase in CL/F by decreasing bioavailability. It has been reported that iron significantly binds to CBZ (2), but this is the first clinical evaluation of a significant effect. The results from this study indicate that use of supplementation of iron may need to be considered when dosing CBZ in the elderly nursing home population and also younger persons receiving this drug. References 1. N. R. Campbell, B. B. Hasinoff, Iron supplements: a common cause of drug interactions. Br J Clin Pharmacol 31, 251-255 (1991). 2. P. Garzon-de la Mora, A. Navarro-Ruiz, J. Garcia-Estrada, E. Correa, Iron binding to anticonvulsants. Arch Invest Med (Mex) 15, 293-301 (1984). Funding: NIH NINDS P50-NS16308 and NIA R01 AG026390