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.

Influence of prokinetics on the gastrointestinal transit and residence times of activated charcoal.

OBJECTIVE: To find the effects of prokinetics, saline cathartics and different charcoal doses on the gastrointestinal transit and residence times of activated charcoal (AC). SETTING: Five undergraduate volunteers of College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, Anambra State, Nigeria, were studied. METHODS: After an overnight fast, the volunteers were given 10 g and 20 g AC with and without saline cathartics, in a simple cross-over design in which the subjects served as their own control. In another experiment, the volunteers received 10 g AC and magnesium sulphate, with propantheline (as bromide 15 mg), metoclopramide (as hydrochloride 10 mg), placebo liquid or identical placebo capsule. Gastrointestinal transit and residence times of AC were recorded. RESULTS: Increase in the dose of AC significantly (P < 0.05) decreased the transit, but not the residence time of AC. Addition of saline cathartics (Na2SO4 and MgSO4) decreased both the transit and residence times of AC significantly (P < 0.05). Also, administration of propantheline, but not metoclopramide, produced a significant (P < 0.05) decrease in both the transit and residence times of AC. The transit and residence times were statistically (P < 0.05) different in both the magnesium sulphate group, as well as in the placebo liquid and placebo capsule groups. CONCLUSION: Cathartic efficiency is enhanced by alteration of gastrointestinal motility with propantheline.

Saline cathartics and adsorptive capacity of activated charcoal for doxycycline.

The effects of sodium chloride and sodium citrate on the in vitro adsorption of doxycycline to activated charcoal have been studied. Solutions of doxycycline alone and doxycycline with 7.5 mg/ml cathartic solutions were vortex-mixed for 30 s with different quantities of activated charcoal, incubated for 30 min at 37 degrees C and analyzed for free doxycycline spectrophotometrically at 348 nm. Addition of NaCl had a significant (p<0.05) increase while sodium citrate produced a significant (p<0.05) decrease in the adsorption of doxycycline on activated charcoal. In all, the adsorption doxycycline on activated charcoal obeyed quantity-dependent kinetics.

Some plasma pharmacokinetic parameters of isoniazid in the presence of a fluoroquinolone antibacterial agent.

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.

Adsorptive capacity of activated charcoal for rifampicin with and without sodium chloride and sodium citrate.

The effects of two saline cathartics (sodium chloride and sodium citrate) on the adsorptive capacity of activated charcoal (AC) for rifampicin were studied. Solutions of rifampicin alone and rifampicin with 7.5 mg/ml cathartic solution were vortex-mixed for 30 s with different quantities of AC. These were incubated for 30 min at 37 degrees C and analyzed for free rifampicin spectrophotometrically at 320 nm. The addition of sodium citrate significantly increased (p<0.05) the adsorptive capacity of AC for rifampicin with a resulting decrease in B-50 values at both the therapeutic and simulated toxic doses. Sodium chloride addition reduced the binding of rifampicin to AC at the toxic doses. The adsorption of rifampicin to activated charcoal, both alone and with the two saline cathartics, obeyed quantity-dependent kinetics. AC may be co-administered with sodium citrate in the management of rifampicin overdose.

Effect of activated charcoal on diethylcarbamazine absorption in humans.

We investigated the effect of the oral binder-activated charcoal on the excretion of diethylcarbamazine. Six healthy volunteers were given 150 mg diethylcarbamazine with 350 mL water each. One and 2 weeks later, they received 150 mg diethylcarbamazine plus 7.5 and 15 g activated charcoal, respectively, in 350 mL water as a charcoal slurry. Urinary levels of diethylcarbamazine were measured spectrophotometrically from 1 to 72 hours after ingestion in three different periods. Treatment with activated charcoal led to 5.4% urinary recovery of diethylcarbamazine, decreased excretion rate, and a much lower plateau indicator of reduced absorption. Activated charcoal reduces the absorption and urinary excretion rate of diethylcarbamazine by adsorbing it in the gastrointestinal tract.

Acceleration of body clearance of diethylCarbamazine by oral activated charcoal.

The effect of activated charcoal (AC) on body clearance of diethylcarbamazine (DEC) was investigated in six healthy volunteers. On three occasions at weekly intervals, each subject received 150 mg of DEC with 350 ml of water. One and two weeks later, 150 mg of DEC plus 7.5 g and 15 g of AC, respectively, in 350 ml of water as a charcoal slurry. The non-renal clearance of DEC expressed as the total body clearance of DEC was increased after treatment with AC. The 45.2, 79.6 percent and 58.6, 81.6 percent reductions in maximum concentration and area under the concentration-time curve, respectively, suggest an appreciable adsorption of DEC by AC (7.5 and 15 g) in the gut. Serum eliminating half-life was decreased upon treatment with AC (7.5 and 15 g). These results indicate that AC accelerates the body clearance of DEC by increasing non-renal elimination of the drug.

Pharmacokinetics of diethylcarbamazine: prediction by concentration in saliva.

The concentration of diethylcarbamazine in saliva was used to determine pharmacokinetic parameters, in comparison to plasma and urine concentrations. Six healthy adult male volunteers were administered 150 mg diethylcarbamazine with 400 ml of water. At seven different time intervals, blood, urine and saliva samples were taken, and different pharmacokinetic parameters measured. The plasma-saliva concentration ratio was calculated as 1.53 whereas the observed ratio was 3.82. The half lives, times to reach peak plasma concentration, and elimination rate constants did not show any significant difference in the different samples. The plasma peak concentration and areas under the curve were significantly (p<0.05) increased from those of the saliva. At 24 h, when diethylcarbamazine was absent in urine, the plasma and saliva concentrations were almost zero. Diethylcarbamazine is secreted in saliva, and its concentration in saliva can be used to monitor drug therapy.

Zinc protection of mercury-induced hepatic toxicity in mice.

The actions and interactions of heavy metals on certain organ functions have been of concern, since occupational exposure to certain metals results in impairment of functions. Studies were carried out to determine the effects of zinc (Zn) and mercury (Hg) on murine liver. CD-1 male mice were administered 4 ppm HgCl2, 800 ppm ZnCl2, 4 ppm HgCl2+800 ppm ZnCl2 or deionized water in their drinking water for 12 weeks. Histological evaluation of the liver confirmed the toxic effects of Hg, as well as the normal morphology of the Zn-exposed animals. A combined treatment of both metals resulted in protection of the Hg-induced liver damage by Zn. The results of this experiment indicate that Hg has a toxic effect on liver, while Zn has a protective action against such toxic effects.