Electronic compliance assessment of antifungal prophylaxis for human immunodeficiency virus-infected women.

Several prophylactic medications for opportunistic or recurrent infections are used in human immunodeficiency virus-infected individuals. Essential to the efficacy evaluation of these agents is the accurate reporting of medication compliance. We hypothesized that poor patient compliance with thrice-weekly fluconazole prophylaxis would correlate with the occurrence of clinical events.

Issues in polypharmacotherapy: focus on major depression.

Combination therapy is often used to improve efficacy, speed response, or attenuate an adverse effect of the initial pharmacotherapy. This article examines key issues in the use of polypharmacotherapy in the treatment of major depressive disorders. The addition of lithium and to a lesser extent triiodothyronine T3 have been shown to be effective augmentation strategies in treatment-resistant depression.

Alopecia associated with zidovudine therapy.

Alopecia has been described in patients infected with the human immunodeficiency virus (HIV). Zidovudine reportedly influences hair growth in these patients, causing regrowth or thickening. A 33-year-old HIV-infected man developed alopecia areata after beginning zidovudine therapy.

Population pharmacokinetics of stavudine (d4T) in patients with AIDS or advanced AIDS-related complex.

The population pharmacokinetics and bioavailability of oral stavudine (d4T; 2',3'-dideoxy-3'-deoxythymidine) was determined in 81 patients with AIDS or AIDS-related complex (ARC) enrolled in phase I and phase I/II dose-ranging trials. Each patient underwent inpatient pharmacokinetic studies following administration of the first oral stavudine dose; 59 patients were restudied after chronic therapy for an average of 19 days. Thirty-three of these patients also received a single intravenous stavudine dose prior to starting an oral regimen.

Management of herpesvirus infections in the healthy host.

Human herpesvirus infections continue to be a concern in immunocompetent as well as immunocompromised hosts. They are often life threatening in the immunocompromised patient. In the healthy immunocompetent person the infections tend to be self-limited, although they can directly or indirectly cause periods of severe discomfort and disability, and their treatment can affect productivity, as shown by cost-outcome models.

Combination beta-lactam and beta-lactamase-inhibitor therapy: pharmacokinetic and pharmacodynamic considerations.

Pharmacokinetic and pharmacodynamic considerations in in vitro susceptibility testing are described, and the integration of pharmacokinetic and pharmacodynamic concepts in dosage-regimen design is explored. Both the amount of beta-lactamase produced per unit of time and the amount of beta-lactamase inhibitor supplied greatly influence susceptibility to beta-lactam antibiotics. The goal should be to supply enough beta-lactamase to render the bacteria functionally beta-lactamase negative.

Clinical pharmacokinetics of nucleoside antiretroviral agents.

The rapid clinical evaluation of new drugs active against human immunodeficiency virus (HIV) requires that pharmacologic properties be carefully considered to determine optimal exposure profiles in patients. The published pharmacokinetic data for the nucleoside antiretroviral agents zidovudine, didanosine, zalcitabine, stavudine, and lamivudine show that administration of fixed doses of certain agents results in a considerable degree of between-patient variability in in vivo drug exposure. Pharmacologic treatment of HIV infection requires development of strategies for individualized adjustment of doses of certain agents with a high degree of interpatient variability.

Issues in polypharmacotherapy: focus on depression in schizophrenia.

The use of polypharmacotherapy in the treatment of psychiatric disorder is commonplace. However, few studies evaluate the safety and efficacy of combination treatments. In general, studies of combinations of drugs are difficult to perform and are not required for approval of medications, nor are they commonly used to justify the almost routine use of combination therapy in daily clinical practice.

Bacterial resistance mechanisms to beta-lactam antibiotics: assessment of management strategies.

Several mechanisms render antimicrobials inactive; one of these, beta-lactamase hydrolysis of beta-lactam antimicrobials, is a common and serious problem resulting in loss of antimicrobial activity. Resistance in gram-negative organisms may be caused by chromosomally or plasmid-mediated beta-lactamases. Chromosomally mediated resistance may result from exposure to inducer compounds (induction) or by selection of stably derepressed mutants.

Pharmacologic evaluation of megestrol acetate oral suspension in cachectic AIDS patients.

The objective of our study was to define the pharmacokinetics and pharmacodynamics of megestrol acetate in patients with human immunodeficiency virus (HIV) infection. A new suspension formulation of megestrol acetate (40 mg/ml) was administered as a single oral dose of 800 mg per day in an open label pharmacokinetic study for 21 days. On day 21 of therapy, patients were evaluated for changes in body weight and plasma samples were obtained for steady-state pharmacokinetic analysis.

Dose ranging and fractionation of intravenous ciprofloxacin against Pseudomonas aeruginosa and Staphylococcus aureus in an in vitro model of infection.

The effect of dose or dose interval on the pharmacodynamics of simulated high-dose intravenous ciprofloxacin therapy on infection due to Pseudomonas aeruginosa and Staphylococcus aureus was studied in an in vitro hollow-fiber model of infection. Simulated doses of 1,200 mg of ciprofloxacin per day as either 400 mg every 8 h or 600 mg every 12 h against P. aeruginosa resulted in selection of ciprofloxacin-resistant bacteria.

In vitro postantibiotic effect following repeated exposure to imipenem, temafloxacin, and tobramycin.

The postantibiotic effect (PAE) following three consecutive 2-h exposures to imipenem, temafloxacin, and tobramycin was determined in Pseudomonas aeruginosa. A PAE and a bactericidal effect were consistently observed for imipenem following each cycle of drug exposure and regrowth. In contrast, the PAE increased with repeated exposure with temafloxacin (1.

Maximizing patient outcomes of antiinfective therapy.

Drug treatment of infectious disease requires consideration of both short- and long-term therapy. Although in most settings patients receive antimicrobials for acute events, long-term management of certain infections with drugs that delay progression of the disease adds a new facet to pharmacotherapy. In the past, broad questions regarding efficacy were posed: a drug was evaluated as either effective or not effective for a particular disorder.

Drug-drug interactions with fluoroquinolones.

Antimicrobials of the fluoroquinolone class are involved in a number of clinically important drug-drug interactions. Many of these interactions occur with all the available agents and exhibit little interpatient variability. In contrast, others occur only with specific fluoroquinolones and their extent varies markedly among subjects.

Thioridazine improves affective symptoms in schizophrenic patients.

Consenting schizophrenic patients ranging in age from 18 to 63 years were withdrawn from antipsychotics for at least 1 week and randomly assigned to receive identical capsules of thioridazine (n = 13), molindone (n = 10), or haloperidol (n = 12) for a minimum of 6 weeks. Compared with the molindone- and haloperidol-treated patients, the thioridazine-treated patients were significantly improved over time as measured by Brief Psychiatric Rating Scale (BPRS) and Hamilton Rating Scale for Depression (HAM-D) total scores. Improvement in BPRS scores was due largely to improvement in symptoms of anxiety and depression.

Pharmacokinetics of stavudine in patients with AIDS or AIDS-related complex.

The pharmacokinetics of stavudine (d4T; 2',3'-didehydro-3'-deoxythymidine) were studied in patients with AIDS-related complex or AIDS enrolled in a dose-ranging phase I/II study. Twenty-two patients were studied after the first oral dose of 0.67, 1.

Interactions of fluoroquinolones with other drugs: mechanisms, variability, clinical significance, and management.

Several important interactions of fluoroquinolones with other drugs have been reported in the literature. The absorption of all fluoroquinolones is almost entirely inhibited by concomitant administration of di- and trivalent cations, such as aluminum and magnesium contained in antacids. The inhibition of absorption can be significant and can potentially lead to the failure of treatment, even when fluoroquinolone doses are separated from antacid doses by hours.

Pharmacokinetics and safety of single rising doses of ofloxacin in healthy volunteers.

The pharmacokinetics, safety, and disposition of the new antimicrobial fluoroquinolone ofloxacin were evaluated after oral administration in 14 healthy, male volunteers in a double-blind, placebo-controlled study. Ofloxacin was administered as 100-, 300-, and 600-mg doses separated by 1 week. Plasma and urine concentrations after each administration were measured using a sensitive and specific high-performance liquid chromatographic procedure.

A review of the pharmacokinetic profile of temafloxacin.

Temafloxacin is a new fluoroquinolone with potent activity against several important bacteria. Studies in healthy volunteers indicate that the average bioavailability of temafloxacin exceeds 90%, with little intersubject variability. Steady-state peak serum levels are approximately 1 mg/L per 100 mg oral dose administered; thus, the steady-state peak serum level after 600 mg bd oral dosing is approximately 6 mg/L.

Combination therapy with ciprofloxacin plus azlocillin against Pseudomonas aeruginosa: effect of simultaneous versus staggered administration in an in vitro model of infection.

The effect of dose scheduling on the pharmacodynamics of simulated human doses of ciprofloxacin (200 mg intravenously [iv] every 12 h) and azlocillin (4 g iv every 12 h) alone or in combination against Pseudomonas aeruginosa was studied in a two-compartment in vitro kinetic model of infection. Studies with the two drugs in combination were compared using simultaneous or staggered (first doses of each drug were administered 6 h apart) dosing schedules. Bacterial regrowth and resistance were prevented by all combination dosing schedules; however, the simultaneous regimen consistently provided the greatest extent of killing for all strains, particularly in those initially resistant to ciprofloxacin.

Pharmacoepidemiology of ciprofloxacin: analysis of use patterns and cost impact.

The pharmacoepidemiology and cost impact of ciprofloxacin use were evaluated after unrestricted availability in a 238-bed community teaching hospital. The medical records on all patients treated with oral ciprofloxacin over 6 months were reviewed. To determine if the availability of ciprofloxacin altered antibiotic usage patterns and outcome variables, a group of control patients from a period prior to ciprofloxacin availability were matched and compared to patients who had received the drug.

The effect of food or milk on the absorption kinetics of ofloxacin.

We have studied the effects of food or milk on the absorption of ofloxacin in 21 healthy male volunteers in a three-way crossover design. Milk did not alter the rate or extent of absorption of ofloxacin or its elimination. Food altered the onset and/or rate of absorption, but not the extent of absorption or the elimination rate.

Pharmacokinetics and bioavailability of intravenous-to-oral enoxacin in elderly patients with complicated urinary tract infections.

The pharmacokinetics of oral fluoroquinolone antibiotics in normal volunteers have been studied extensively; however, limited patient data exist. Enoxacin steady-state pharmacokinetics and bioavailability were determined following repeated 400-mg intravenous (i.v.