Effect of chloroquine on the bioavailability of ciprofloxacin in humans.

Chloroquine, a front-line drug in the treatment of malaria, has developed widespread resistance, especially to the Plasmodium falciparum strains. Ciprofloxacin is a second-generation quinolone used as a broad-spectrum fluoroquinolone antibacterial agent. The possibility of using ciprofloxacin as an antimalarial, especially in chloroquine-resistant strains, is very promising. They concluded from in vitro studies however that the anti-malarial effect occur at high dose level of ciprofloxacin to achieve the required serum concentrations. Studies have shown that there is little interstrain variability in the in vitro susceptibility of P. falciparum to fluoroquinolones. There is also no cross-resistance between them. Another study stated that 50% inhibition of parasite growth in vitro required 6.6 microg/mL after a high dose of ciprofloxacin was used. They thus concluded that ciprofloxacin should not be used alone. There is need for in vivo studies to ascertain the achievable serum concentration of ciprofloxacin when given alone and when given in combination with chloroquine. The serum concentration of ciprofloxacin was studied when ciprofloxacin was given alone and in combination with chloroquine in humans. Five healthy male volunteers aged (19-31) years who were not taking any of the prescribed medications and had no sensitivity to either ciprofloxacin or chloroquine, each received 500 mg ciprofloxacin orally with 250 mL of water, and after a 2-week wash-out period, 500 mg ciprofloxacin plus 600 mg of chloroquine was administered orally with 250 mL of water after informed consent. A blood sample (2.5 mL) was collected just before taking the drug at 8:00 AM representing 0 hours and continued afterward at 1, 2, 4, 8, 12, and 24 hours the following day. Serum samples were stored at -20 degrees C until analyzed. The minimal inhibitory concentrations (MIC) by diffusion through agar technique was used for the assay of serum ciprofloxacin. The following bioavailability parameters: Cmax, tmax, and AUC 0-24, AUC 0-infinity were calculated. The peak serum concentration Cmax of ciprofloxacin was 3.42 +/- 0.32 microg/mL, which dropped to 2.8 +/- 0.18 microg/mL when chloroquine was taken together with ciprofloxacin. These values were less than the in vitro 12.5 microg/mL concentrations required to inhibit P. falciparum. Though the effect of parasitemia was not ascertained, the in vivo use of ciprofloxacin alone or in combination is doubtful because increasing the dose that will reach the in vitro level will lead to toxicity in vivo.