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The bioequivalence of oral administration of telithromycin tablets crushed versus swallowed whole in healthy adult subjects
Author(s) -
Lippert C. L.,
Gbenado S.,
Qiu C.,
Lavin B.,
Kovacs S. J.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.081
Subject(s) - bioequivalence , telithromycin , cmax , geometric mean , crossover study , medicine , pharmacokinetics , oral administration , pharmacology , mathematics , placebo , statistics , alternative medicine , clarithromycin , pathology , helicobacter pylori
Background/Aim To establish bioequivalence of telithromycin (TEL) crushed versus whole tablet administration. Methods Open‐label, single‐dose, randomized, 2‐period, crossover study with a 6‐day washout between periods: Treatment A: TEL 800 mg (2× 400‐mg tablets), swallowed whole with 240 mL water; Treatment B: TEL 800 mg (2× 400‐mg tablets), crushed and mixed in 240 mL Ensure ® , followed by 120 mL water. Blood samples were collected predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hpostdose. Plasma was assayed for TEL concentration by LC/MS/MS. Exposure measures were computed by noncompartmental methods using WinNonlin ® (Pharsight Corporation). C max and AUC (0–24) were determined from observed data. Average bioequivalence criteria was applied. Results 32 subjects (16 M, 16 F) completed the study. 90% confidence intervals for the mean ratio of AUC (0–24) and C max were within the 0.80–1.25 range. Median T max was also similar between treatments (3.00 hours for each treatment). Both methods of administration were safe and generally well tolerated. Conclusions Crushing telithromycin tablets administered with Ensure is bioequivalent to administration of whole tablets. Breaking or crushing telithromycin tablets can be a viable alternate method of administration for patients unable to swallow whole tablets. (see Table) Clinical Pharmacology & Therapeutics (2005) 77 , P49–P49; doi: 10.1016/j.clpt.2004.12.081Geometric Least Squares Mean Mean Ratio (Treatment B/Treatment A)Whole (Treatment A) Crushed (Treatment B) Estimate 90 CIN 32 32 ‐ ‐ AUC (0–24) (μg·h/mL) 7.493 7.862 1.049 (0.966, 1.139) C max (μg/mL) 1.324 1.255 0.947 (0.854, 1.051)AUC 0–24 = area under the concentration time curve from 0 to 24h; CI= confidence interval; C max = peak concentration.