Pharmacokinetics of ethambutol in children and adults with tuberculosis.

Setting: Five hospitals in the United States.

Objective: To describe ethambutol pharmacokinetics in children and adults with active tuberculosis (TB).

Design: Prospective, open-labeled study in 56 adults and 14 children with active tuberculosis who received ethambutol as part of their multidrug TB regimens.

Guidelines for using darbepoetin alfa in patients with chemotherapy-induced anemia.

Anemia is an undertreated but common complication of cancer and is associated with debilitating symptoms that impair the patient's ability to perform daily functions of life. Treatment with darbepoetin alfa, a novel erythropoiesis-stimulating protein, is appropriate for chemotherapy-induced anemia. Guidelines on darbepoetin alfa therapy will assist clinicians in its appropriate application.

Population pharmacokinetics of intravenous and intramuscular streptomycin in patients with tuberculosis.

Study Objectives: To determine population pharmacokinetic parameters of streptomycin after administration of multiple intramuscular and intravenous doses.

Design: Prospective, unblinded clinical study.

Setting: Two medical centers in Denver, Colorado.

Etiology of neutropenia in HIV-infected patients.

The causes of neutropenia in HIV-infected patients are described, as is the association of absolute neutrophil count (ANC) and the risk of bacterial infections. In patients with HIV infection, neutropenia can result from the disease or related malignancies, drug therapies, or opportunistic infections. HIV can cause neutropenia by directly or indirectly impairing hematopoiesis.

Pharmacokinetics of ethambutol under fasting conditions, with food, and with antacids.

Ethambutol (EMB) is the most frequent "fourth drug" used for the empiric treatment of Mycobacterium tuberculosis and a frequently used drug for infections caused by Mycobacterium avium complex. The pharmacokinetics of EMB in serum were studied with 14 healthy males and females in a randomized, four-period crossover study. Subjects ingested single doses of EMB of 25 mg/kg of body weight under fasting conditions twice, with a high-fat meal, and with aluminum-magnesium antacid.

Pharmacokinetics of pyrazinamide under fasting conditions, with food, and with antacids.

Study Objectives: To determine intrasubject and intersubject variability in, and the effects of food and antacids on, the pharmacokinetics of pyrazinamide (PZA).

Design: Randomized, four-period, crossover phase I study.

Subjects: Fourteen healthy men and women volunteers.

Population pharmacokinetic modeling of isoniazid, rifampin, and pyrazinamide.

Isoniazid (INH), rifampin (RIF), and pyrazinamide (PZA) are the most important drugs for the treatment of tuberculosis (TB). The pharmacokinetics of all three drugs in the plasma of 24 healthy males were studied as part of a randomized cross-over phase I study of two dosage forms. Subjects ingested single doses of INH at 250 mg, RIF at 600 mg, and PZA at 1,500 mg.

Pneumocystis carinii pneumonia in HIV infected patients: effects of the diseases on glutathione and glutathione disulfide.

Human immunodeficiency virus (HIV) infection is associated with altered levels of glutathione (GSH) in cells and extracellular fluids. GSH is essential for lymphocyte proliferation and inhibits HIV replication. Therefore, determination of GSH and glutathione disulfide (GSSG) levels could be useful as indicators of the progression of the disease.

Serum and blister fluid pharmacokinetics and bactericidal activities of ampicillin-sulbactam, cefotetan, cefoxitin, ceftizoxime, and ticarcillin-clavulanate.

Ampicillin-sulbactam, ticarcillin-clavulanate, cefoxitin, cefotetan, and ceftizoxime are promoted for the treatment of mixed aerobic-anaerobic bacterial infections. Their activities have been compared in vitro but not in vivo. In order to assess the in vivo activities of these agents in serum and interstitial fluid, we administered single, intravenous doses of these antimicrobial agents to healthy subjects.

Imipenem pharmacokinetics in patients with burns.

The pharmacokinetics of imipenem were studied in 11 adult patients with severe burns who were receiving a therapeutic regimen of imipenem-cilastatin 500 mg intravenously every 6 hours. Serial blood samples for measuring imipenem and 24-hour urine collections for creatinine clearance (CrCl) were obtained after the initial dose and after multiple dosing. Plasma was assayed for imipenem by use of HPLC.

Phenytoin pharmacokinetics in critically ill trauma patients.

Preliminary data have suggested that phenytoin systemic clearance may increase during initial therapy in critically ill patients. The objectives for this study were to model the time-variant phenytoin clearance and evaluate concomitant changes in protein binding and urinary metabolite elimination. Phenytoin was given as an intravenous loading dose of 15 mg/kg followed by an initial maintenance dose of 6 mg/kg/day in 10 adult critically ill trauma patients.

Imipenem monotherapy versus combination therapy in the management of mixed bacterial infection: a critical appraisal.

There has been a great deal of interest in the use of imipenem monotherapy rather than combinations of antimicrobials for mixed bacterial infections. A review of the published comparative studies of imipenem versus combinations in serious mixed bacterial infections indicated that, overall, imipenem is at least as effective as, and maybe less expensive than, the combinations tested. Several studies suggest that clinical response to imipenem is more rapid than to the comparison regimens; however, other factors may have influenced these values, and the numbers of patients in these reports were small.

Rapid adjustment of theophylline: a kinetic model.

This study was designed to test the validity and applicability of basic kinetic equations to describe theophylline disposition. The method involves early determination of clearance from a nonsteady-state level, dosage adjustment on the basis of the estimated clearance, and measurement of serum theophylline concentration at a point very near steady state. To test the method, a 32-patient study group was examined.