BACKGROUND:Levetiracetam (LEV) is an antiepileptic drug with a favorable pharmacokinetic profile, including negligible protein binding and linear elimination kinetics. Because LEV is likely to be used in populations that include children and the elderly, alternative techniques of administration, such as crushing the tablet and mixing its contents with semisolid food or enteral nutrition formulas (ENFs), may be required in some clinical settings. Although previous studies have suggested that administration with food does not affect the overall absorption of LEV, there is a lack of data regarding concomitant administration with ENFs. OBJECTIVE: The objective of this study was to evaluate the oral absorption of LEV after concomitant administration with food or ENFs. METHODS: This was an unblinded, 3-way crossover study. After an overnight fast, subjects received a single dose of LEV 500 mg administered either as an intact tablet with 120 mL water (control, treatment A) or crushed and mixed with 4 oz applesauce (treatment B) or 120 mL of a common ENF (treatment C). All subjects received each treatment in a randomized sequence; there was a 7-day washout period between treatments. Serial blood samples were obtained over 24 hours for determination of the LEV serum concentration-time profile using gas chromatography with nitrogen phosphorus detection. AUC(0-24), C(max), and T(max) were calculated using noncompartmental methods and analyzed using analysis of variance. RESULTS:Ten healthy adult volunteers (6 men, 4 women) participated in the study (mean [SD] age, 28.9 [6.5] years; mean body weight, 78.6 [12.9] kg). No significant differences were noted between control and any other study treatment. Mean AUC values were 191.9 (50.2), 165.7 (43.4), and 168.3 (43.9) microg/mL . h for treatments A, B, and C, respectively. Mean T(max) values were 1.08 (0.65), 1.32 (0.75), and 1.62 (0.73) hours, respectively. Mean C(max) values were 14.8 (5.6), 12.1 (2.8), and 10.8 (2.0) microg/mL for the respective treatments. Mean LEV serum concentrations at 12 hours after dosing were similar for all study treatments (3.9, 4.1, and 4.0 microg/mL). The long-term stability of LEV in the various combinations was not assessed. CONCLUSIONS: In these healthy volunteers, the overall rate and extent of absorption of oral LEV were not significantly impaired after crushing and mixing of the tablet with either a food vehicle or a typical ENF product. The data suggest that peak serum concentrations of LEV may be slightly reduced after mixing with ENFs, although the difference was not significant compared with control values.
RCT Entities:
BACKGROUND:Levetiracetam (LEV) is an antiepileptic drug with a favorable pharmacokinetic profile, including negligible protein binding and linear elimination kinetics. Because LEV is likely to be used in populations that include children and the elderly, alternative techniques of administration, such as crushing the tablet and mixing its contents with semisolid food or enteral nutrition formulas (ENFs), may be required in some clinical settings. Although previous studies have suggested that administration with food does not affect the overall absorption of LEV, there is a lack of data regarding concomitant administration with ENFs. OBJECTIVE: The objective of this study was to evaluate the oral absorption of LEV after concomitant administration with food or ENFs. METHODS: This was an unblinded, 3-way crossover study. After an overnight fast, subjects received a single dose of LEV 500 mg administered either as an intact tablet with 120 mL water (control, treatment A) or crushed and mixed with 4 oz applesauce (treatment B) or 120 mL of a common ENF (treatment C). All subjects received each treatment in a randomized sequence; there was a 7-day washout period between treatments. Serial blood samples were obtained over 24 hours for determination of the LEV serum concentration-time profile using gas chromatography with nitrogen phosphorus detection. AUC(0-24), C(max), and T(max) were calculated using noncompartmental methods and analyzed using analysis of variance. RESULTS: Ten healthy adult volunteers (6 men, 4 women) participated in the study (mean [SD] age, 28.9 [6.5] years; mean body weight, 78.6 [12.9] kg). No significant differences were noted between control and any other study treatment. Mean AUC values were 191.9 (50.2), 165.7 (43.4), and 168.3 (43.9) microg/mL . h for treatments A, B, and C, respectively. Mean T(max) values were 1.08 (0.65), 1.32 (0.75), and 1.62 (0.73) hours, respectively. Mean C(max) values were 14.8 (5.6), 12.1 (2.8), and 10.8 (2.0) microg/mL for the respective treatments. Mean LEV serum concentrations at 12 hours after dosing were similar for all study treatments (3.9, 4.1, and 4.0 microg/mL). The long-term stability of LEV in the various combinations was not assessed. CONCLUSIONS: In these healthy volunteers, the overall rate and extent of absorption of oral LEV were not significantly impaired after crushing and mixing of the tablet with either a food vehicle or a typical ENF product. The data suggest that peak serum concentrations of LEV may be slightly reduced after mixing with ENFs, although the difference was not significant compared with control values.
Authors: Elizabeth Greiner-Sosanko; Spiros Giannoutsos; Darla R Lower; Mohamed A Virji; Matthew D Krasowski Journal: J Chromatogr Sci Date: 2007-10 Impact factor: 1.618