The effects of ciprofloxacin (CP), a fluoroquinolone antibacterial agent, on the extent of absorption of isoniazid (INH) and on some of its pharmacokinetic parameters were investigated in six healthy female volunteers between the ages of 23 and 32 years. The presence of CP led to increase in the amount of INH and to a slight reduction in its peak plasma concentration (Cmax). There was a 1-hour increase in the time to attain Cmax (tmax) of INH, indicating absorption interaction between the two drugs. This absorption interaction was related to inhibition of cholinergic neurotransmission caused by CP, which is capable of inhibiting gastric motility, leading to a delay in gastric emptying. The rate of elimination (K) and plasma half-life (t1/2) of INH were not significantly affected (P = 0.05). The extent of absorption interaction that may have occurred (based on values of 24-hour values for area under the concentration curve, Cmax, Tmax, K, and t1/2) was considered to be of no therapeutic consequence, and the coadministration of the two drugs may be recommended in clinical practice.

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.