Jan Sahai

Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers.

Cations such as magnesium and aluminum significantly impair the absorption of ciprofloxacin. Twelve healthy adult male volunteers participated in this four-way crossover study to investigate the effects of ferrous sulfate and multivitamins with zinc on the absorption of ciprofloxacin. Doses of ciprofloxacin (500 mg) were given 7 days apart and after an overnight fast. Dose 1 was administered alone (regimen A). The subjects then received either a ferrous sulfate tablet (325 mg three times a day; regimen B) or a once-daily multivitamin with zinc (regimen C) for 7 days; dose 2 of ciprofloxacin was then given with the last dose of regimen B or C. Subjects were crossed over to the alternate regimen for 7 days, and dose 3 of ciprofloxacin was again administered with the last dose of regimen B or C. After a 7-day washout, dose 4 of ciprofloxacin was given (regimen D). Ciprofloxacin concentrations were determined by high-pressure liquid chromatography. The areas under the concentration-time curve (AUCs) of ciprofloxacin for regimens A and D were not significantly different (14.5 +/- 2.3 versus 15.7 +/- 2.8 micrograms.h/ml, mean +/- standard deviation). The AUCs for regimen B (5.4 +/- 1.7 micrograms.h/ml) and regimen C (11.3 +/- 2.4 micrograms.h/ml) were significantly different from the AUCs for regimens A and D. Peak concentrations of ciprofloxacin with regimen B were below the MIC for 90% of strains of many organisms normally considered susceptible. Ferrous sulfate and multivitamins with zinc significantly impaired the absorption of ciprofloxacin. The effect of ferrous sulfate is likely to be clinically significant; the responsible component of multivitamins with zinc requires additional study.

Eflornithine for the Treatment of Pneumocystis carinii Pneumonia in Patients with the Acquired Immunodeficiency Syndrome: A Preliminary Review

Pneumocystis carinii pneumonia (PCP) is the most common opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS). Eflornithine is an antiprotozoal agent active against P. carinii. It acts by inhibiting ornithine decarboxylase, an enzyme that is essential for cellular function. The drug is initially administered intravenously, followed by oral therapy. Eflornithine has been used on a compassionate basis in AIDS patients with PCP who were intolerant of or unresponsive to traditional agents. Overall, the response rate has been about 35%; however, conclusions are difficult to make since patients had different stages of disease and received treatment for varying periods of time. Side effects include depression of bone marrow function, diarrhea, hearing loss, seizures, alterations in liver function tests, and rash. While the need for safer and more efficacious antipneumocystis drugs grows, widespread use of seemingly promising agents should be based on well‐conducted clinical trials.

Effect of antacids in didanosine tablet on bioavailability of isoniazid.

The antacids in two didanosine placebo tablets had no significant effect on the plasma pharmacokinetics of a single oral dose of 300 mg of isoniazid administered to 12 healthy volunteers. These results suggest that isoniazid bioavailability will be unaffected by the antacids in didanosine tablets when the two medications are administered simultaneously to human immunodeficiency virus-seropositive patients.

Influence of an antacid containing aluminum and magnesium on the pharmacokinetics of cefixime.

Interaction studies in dogs have indicated that antacids significantly decrease the oral bioavailability of cefixime. Twelve healthy adult male volunteers participated in a randomized, four-way crossover trial to evaluate the influence of an aluminum-magnesium antacid (Maalox; 20 ml) on the pharmacokinetics of cefixime (400 mg). Regimens were (i) cefixime alone; (ii) cefixime simultaneous with antacid; (iii) cefixime 2 h before antacid; and (iv) cefixime 2 h after antacid. Serial blood and urine samples were collected over a 24-h period following each dose of cefixime. There was a 1-week washout interval between regimens. Cefixime concentrations in serum and urine were analyzed by high-performance liquid chromatography. Maximum cefixime concentrations in serum for regimens i through iv were (mean +/- standard deviation) 4.9 +/- 1.4, 5.7 +/- 1.3, 5.1 +/- 1.0, and 5.5 +/- 1.5 micrograms/ml, respectively. Corresponding values for area under the serum concentration-time curve extrapolated to infinity were 38.3 +/- 14.5, 42.8 +/- 13.9, 38.5 +/- 9.8, and 41.6 +/- 16.7 micrograms.h/ml. There was a trend toward increased concentrations in serum and area under the curve of cefixime when it was administered concomitantly with antacid; however, these differences were not statistically significant (P greater than 0.05; analysis of variance). We conclude that single-dose administration of an aluminum-magnesium antacid does not significantly decrease the oral bioavailability of cefixime.

Pharmacokinetics of simultaneously administered zidovudine and didanosine in HIV-seropositive male patients.

Our objective was to determine whether a pharmacokinetic interaction exists between zidovudine and didanosine when they are coadministered. This was designed as a randomized, three-period, three-treatment, six-sequence, crossover study with a 1-week washout period between treatments. The patients were six men infected with human immunodeficiency virus who were asymptomatic. On three separate occasions, patients received zidovudine alone (200 mg every 8 h) for 3 days, didanosine alone (200 mg every 12 h) for 3 days, or zidovudine and didanosine for 3 days. On the fourth day, each patient received the final dose of each regimen, and blood and urine were serially collected for 8 h. Pharmacokinetic parameters were assessed for zidovudine, its glucuronide metabolite (GZDV), and didanosine. Coadministration of zidovudine had no significant effect on didanosine pharmacokinetic parameters (< 12% difference between treatment means, p > 0.1). Coadministration of didanosine did not significantly alter zidovudine pharmacokinetic parameters but did cause statistically significant increases in the renal and apparent formation clearances of GZDV (18.5% and 30.5% difference between the treatment means, respectively, p < 0.025). Therapeutic doses of zidovudine did not alter didanosine pharmacokinetic parameters. Coadministration of didanosine did not affect zidovudine parameters but did cause small alterations in GZDV pharmacokinetic values. These changes are unlikely to be clinically significant.

Effect of bismuth subsalicylate on ciprofloxacin bioavailability.

A single oral dose of 528 mg of bismuth subsalicylate (30 ml of Pepto-Bismol) had no significant effect on the plasma pharmacokinetics of a single oral dose of 750 mg of ciprofloxacin administered to 12 healthy volunteers (six men and six women). These results suggest that ciprofloxacin bioavailability will not be significantly decreased by single doses of bismuth subsalicylate when the two medications are administered simultaneously.