DOSE FORMULATION AFFECTS ORAL BIOAVAILABILITY OF ISONIAZID (INH):

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.