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Chloroquine reduces urinary excretion of cloxacillin when it is administered concurrently with ampicillin-cloxacillin combination
Abstract
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 between the drug administrations. Total urine voided was collected from each volunteer at predetermined time intervals for a period of 9 hr. The urine was analyzed for cloxacillin by a reversed-phase HPLC method.
Results: A significant reduction in the amount of cloxacillin excreted in urine was observed following the co-administration of chloroquine and the ampicillin-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 half-life (t1/2) of cloxacillin were 2.7 ± 0.4 hr 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 drugs. The results showed 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 this interaction and possible therapeutic implication is unknown. However, caution should be exercised when prescribing or administering these two drugs together.
Key words: Drug-drug interaction, bioavailability, chloroquine, cloxacillin
Tropical Journal of Pharmaceutical Research 2003; 2(1): 169-173
