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Salivary and Urinary Excretion and Plasma–Saliva Concentration Ratios of Isoniazid in the Presence of Co-administered Ciprofloxacin

Salivary and urinary excretion and plasma–saliva concentration ratios of isoniazid (INH) in the absence and presence of ciprofloxacin (CP) were investigated in healthy female volunteers. Results obtained indicated an absorption form of interaction between INH and CP. This led to delay in gastric emptying and onset of absorption of INH in the upper part of the gastrointestinal tract, resulting in a corresponding delay in the onset of salivary and urinary excretion of the drugs. There was a 1-hour reduction in the time to attain peak saliva concentration of INH (tmax), an insignificant difference in peak saliva concentration (Cmax), and a significant (P = 0.05) increase in AUC(0–24h) of INH in the presence of CP. Cumulative amount of INH excreted in the urine increased approximately 38% in the presence of CP. The calculated plasma–saliva concentration ratios of INH were reduced in the presence of CP and were slightly lower than the experimental values. This indicates increased amount of the drug secreted into saliva in the presence of CP and possible buccal partitioning of the drug. Overall, results of the current study indicate that CP delayed the onset but not the extent of INH absorption. Therefore, concurrent administration of the two drugs was considered relatively safe, and the absorption interaction that may have occurred may not be of reasonable clinical consequence.