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Purpose: To investigate a possible e ffect of chloroquine on urinary excretion o f cloxacillin when chloroquine is administered concurrently with ampicillin-cloxacillin combination. Methods: Eight healthy adult volunteers received single oral doses of Ampiclox ® (ampicillin- cloxacillin combination) alone and in combination with chloroquine in a cross-over study design with one week washout period be tween the d rug ad ministrations. Total urine voided was c ollected from each volunteer at predetermined time intervals for a pe riod o f 9 h r. The urine was analyzed for cloxacillin by a reversed-phase HPLC method. Results: A significant reduction in the a mount of cloxacillin e xcreted in u rine was observed following the co-administration o f chloroquine and the a mpicillin-cloxacillin combination products. The mean total amount of cloxacillin (Du ∞ ), maximum peak of excretion (Dumax) and % dose excreted after Ampliclox ® was administered alone were 84.6 ± 57.0 mg, 49.5 ±41.6 mg and 33.9 ± 22.7% respectively. The corresponding values after co-administration with chloroquine were 30.2 ± 27.2 mg, 13.5 ± 10.4 mg and 12.1 ±10.9%. The respective times of maximum absorption (Tmax) and elimination ha lf-life (t1/2) of cloxacillin were 2.7 ± 0.4 h r and 0.7 ± 0.4 hr after Ampiclox ® alone and 1.5 ± 0.8 hr and 0.6 ± 0.5 hr after co-administration of the two d rugs. The results s howed a significant decrease (p < 0.0001) in the mean total amount as well as % dose of cloxacillin excreted in urine by 64% and a significant reduction (p < 0.05) in the Tmax of excretion by 45%. Conclusion: There is appreciable reduction in the urinary excretion of cloxacillin when given concurrently with chloroquine. The mode of t his interaction and possible therapeutic implication is unknown. However, caution should be exercised when prescribing or administering these two drugs together.

Chloroquine reduces urinary excretion of cloxacillin when it is administered concurrently with ampicillin-cloxacillin combination