Abstract
Children too young to ingest an intact tablet of INH are frequently given untested formulations of the drug, since the commercial liquid syrup (P-I-N Forte, Lannett: INH 50 mg & pyridoxine HCL 2.5 mg in 5 ml) (SYR) is neither widely available nor frequently mentioned in pediatric literature. INH has been orally administered after mixing crushed tablets with foodstuffs, or placing the parenteral dosage form (a clear solution) in a vehicle of fruit juice. The oral bioavailability of these formulations has not been previously studied. We examined 4 children (5-20 months) with tuberculosis. Each received 10 mg/kg test doses of different INH preparations on successive days:1)IM injection(IM,N=4); 2)Oral syrup(SYR, N=3); 3)Crushed tablet mixed with applesauce(TAB,N=4); 4)parenteral solution in applejuice(SOL,N=3). The serum concentration of INH was determined at several intervals after the test doses. For each formulation, the range and means (x) of peak concentrations (ug/ml) were: 1)IM 5.8-11.4 x=7.7; 2)SYR 5.6-8.3, x=6.9; 3)TAB 0.9-3.7, x=2.1; 4)SOL 2.5-3.3, x=3.0. After TAB, peak concentration occurred later (about 2 hours) than after SYR (1 hour or less). The mean area under time-concentration curve (AUC) was lower after TAB (12 ug/ml· hrs)than after IM (21 ug/ml· hrs), indicating limited absorption of this preparation.
Peak levels achieved after administration of TAB were lower and more variable than after administration of SYR or as reported by others after ingestion of intact tablets. Administering a crushed tablet of INH in applesauce does not reliably produce therapeutic serum concentrations of INH in children.
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Notterman, D., Nardi, M. & Saslow, J. DOSE FORMULATION AFFECTS ORAL BIOAVAILABILITY OF ISONIAZID (INH). Pediatr Res 18 (Suppl 4), 157 (1984). https://doi.org/10.1203/00006450-198404001-00385
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DOI: https://doi.org/10.1203/00006450-198404001-00385