Safe use of the CXCR4 inhibitor ALX40-4C in humans.

ALX40-4C is a small peptide inhibitor of the chemokine receptor CXCR4 that can inhibit X4 strains of HIV-1. Prior to the discovery of chemokine receptors as the HIV coreceptors, ALX40-4C was used in phase I/II clinical trials to evaluate its therapeutic potential against HIV-1, making ALX40-4C the first anticoreceptor inhibitor to be tested in humans against HIV-1. Patients in the highest dose groups achieved ALX40-4C levels above the effective concentration of the drug for nearly the entire 1-month treatment period.

Induction of zidovudine glucuronidation and amination pathways by rifampicin in HIV-infected patients.

Aims: The objective of the study was to determine the effect of multiple doses of rifampicin on the steady-state pharmacokinetics of zidovudine and its 5'-glucuronosyl (GZDV) and 3'-amino (AMT) metabolites.

Methods: Eight asymptomatic HIV-infected patients (seven male, one female) participated in this three-period longitudinal study. Each patient received zidovudine (200 mg every 8 h) for 14 days (period 1), followed by rifampicin (600 mg every 24 h) with zidovudine for 14 days (period 2), and then zidovudine alone for a further 14 days (period 3).

Development of an enzyme-linked immunosorbent assay for measurement of serum-associated ALX40-4C.

ALX40-4C is an antiretrovirus agent that has been found to have some inhibitory properties against human immunodeficiency virus (HIV) replication in vitro. The compound was designed as a competitor of the HIV Tat protein for TAR binding. In addition to its anti-HIV properties, it has demonstrated the ability to inhibit in vitro replication of herpes simplex virus types 1 and 2 as well as human cytomegalovirus.

Reduced plasma concentrations of antituberculosis drugs in patients with HIV infection.

Background: Reports suggest that antituberculosis drugs are malabsorbed in patients with advanced HIV disease.

Objective: To evaluate the pharmacokinetics of antituberculosis agents in HIV-seropositive patients at different stages of disease.

Design: Parallel study.

Pharmacokinetics of antimycobacterial drugs in patients with tuberculosis, AIDS, and diarrhea.

To test the hypothesis that antituberculous drug disposition is altered in patients with AIDS, we studied the steady-state pharmacokinetics of isoniazid (300 mg/d), rifampin (600 mg/d), and pyrazinamide (1,500 mg/d) in 29 adults (14 patients infected with human immunodeficiency virus [HIV] and 15 non-HIV-infected patients) with tuberculosis in Nairobi, Kenya. Intestinal integrity was assessed with xylose. Neither HIV infection nor diarrhea accounted for the interpatient variability in the area-under-the-plasma concentration vs.

Rifabutin absorption in the gut unaltered by concomitant administration of didanosine in AIDS patients.

Didanosine (ddI) is currently used in the management of patients infected by the human immunodeficiency virus. Rifabutin (RBT) is being extensively used for prophylaxis against Mycobacterium avium complex (MAC) infections. Due to its acid-labile characteristics, ddI must be administered with a buffer.

Risks and synergies from drug interactions.

Aim: To review what is known from in vitro and in vivo studies about the interactions, both potentially beneficial and potentially harmful, of antiretroviral agents with each other and with other classes of drugs.

Interactions With Nucleoside Analogues: Some interactions between nucleoside HIV reverse transcriptase inhibitors and between nucleoside analogues and HIV protease inhibitors result in greater antiretroviral activity (e.g.

Lack of gender effect on ciprofloxacin pharmacokinetics in humans.

The influence of gender on the single-dose pharmacokinetics of oral ciprofloxacin was investigated in a parallel designed study in 24 healthy, fasted volunteers. Ciprofloxacin (750 mg) was administered as a single tablet to 10 women and 14 men. All subjects were Caucasian except for one African American man.

Effects of the antacids in didanosine tablets on dapsone pharmacokinetics.

Objective: To investigate 1) the effects of the magnesium-aluminum antacids in didanosine tablets on dapsone absorption in healthy volunteers and 2) the effects of the antacid formulation of active didanosine tablets on dapsone pharmacokinetics in patients seropositive for human immunodeficiency virus (HIV).

Design: Two separate, randomized, two-period, two-treatment, crossover studies with a 21-day washout period between treatments.

Setting: Clinical investigation unit of a university hospital.

Effect of rifabutin on the pharmacokinetics of zidovudine in patients infected with human immunodeficiency virus.

We investigated the effects of rifabutin (300 mg daily administered for 7 or 14 days) on the pharmacokinetics of zidovudine in nine patients who were infected with human immunodeficiency virus (HIV). Serial blood and urine samples were collected over a 6-hour period on each day that the pharmacokinetics of zidovudine were studied. Pharmacokinetic parameters were determined for zidovudine and its glucuronide metabolite and compared with use of analysis of variance (ANOVA) appropriate for a repeated-measures design.

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.

A phase I evaluation of concomitant rifabutin and didanosine in symptomatic HIV-infected patients.

It has been suggested that didanosine (ddI) may undergo hepatic metabolism. Rifabutin is an inducer of drug metabolism. Fifteen human immunodeficiency virus-infected patients whose conditions were stabilized on twice-daily doses of ddI participated in a Phase I, open-label, pharmacokinetic and safety drug interaction study between rifabutin and ddI.

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.

Relationship between body weight, body surface area and serum zidovudine pharmacokinetic parameters in adult, male HIV-infected patients.

Objective: To determine whether there is a simple relationship between body weight or body surface area (BSA) and serum zidovudine pharmacokinetic parameters in patients receiving oral zidovudine.

Design: Single-dose, pharmacokinetic study.

Patients: Fifty-three asymptomatic and symptomatic HIV-infected men (CD4+ cell count < 500 x 10(6)/l) participated in the study.

Effect of fluconazole on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus.

The effect of a therapeutic dose of fluconazole on the disposition of zidovudine was evaluated in 12 men infected with human immunodeficiency virus. The study was designed as a randomized, two-period, two-treatment, crossover trial. On two occasions, 21 days apart, patients received either zidovudine alone or zidovudine (each, 200 mg every 8 h) and fluconazole (400 mg daily) for 7 days.

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.

Pharmacokinetics of zidovudine after the initial single dose and during chronic-dose therapy in HIV-infected patients.

The pharmacokinetics of zidovudine in 10 symptomatic HIV-infected men were assessed after administration of the initial 200 mg oral dose at the start of therapy (day 1) and on one occasion during non steady-state conditions of chronic-dose therapy (200 mg every 4 h while awake on day 21-66; 5 doses per day). The following mean (+/- s.d.

Overview of the immune and hematopoietic systems.

Current knowledge of the immune and hematopoietic systems is reviewed. All blood cells are derived from the totipotent stem cell, also known as the pluripotent stem cell. The differentiation of pluripotent peripheral stem cells into blood cells is controlled by a variety of biologic response modifiers, including colony-stimulating factors (CSFs) and interleukins.

The influence of chronic administration of calcium carbonate on the bioavailability of oral ciprofloxacin.

Six healthy male volunteers participated in a two-period, two-treatment study to determine the effect of chronic calcium carbonate administration on ciprofloxacin bioavailability. There was a mean reduction of 40% in Cmax and 43% in AUC when calcium carbonate was administered with ciprofloxacin, compared with ciprofloxacin alone (P < 0.05).

Cations in the didanosine tablet reduce ciprofloxacin bioavailability.

The effect of the magnesium-aluminum cations contained in didanosine chewable tablets on ciprofloxacin pharmacokinetics was evaluated in 12 healthy volunteers. The study was designed as a randomized, balanced, open, two-period, two-treatment crossover trial with a 7-day washout period between treatments. In one phase, subjects received a single 750 mg ciprofloxacin tablet alone.

Evaluation of the in vivo effect of naproxen on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus.

Objective: To determine if therapeutic doses of naproxen affect the in vivo disposition of zidovudine.

Methods: This was designed as a randomized, two-period, two-treatment, crossover study. The patients were 12 men infected with human immunodeficiency virus who had acquired immunodeficiency syndrome (AIDS) or AIDS-related complex.

The effect of a protein meal on zidovudine pharmacokinetics in HIV-infected patients.

Eleven HIV-infected men participated in a randomized, two-treatment, two-period crossover study to determine the effect of a 25 g protein meal on zidovudine pharmacokinetics. On two separate occasions, 1 week apart, each patient received 200 mg zidovudine in a fasting state or immediately following the protein meal. A protein meal significantly decreased Cmax [532 (228 s.

Pharmacokinetics of single and chronic dose zidovudine in two HIV positive patients undergoing continuous ambulatory peritoneal dialysis (CAPD).

The effect of continuous ambulatory peritoneal dialysis (CAPD) on zidovudine (ZDV) elimination was studied in two HIV-positive men. Serum and dialysate samples were collected after a single oral dose of 200 mg (patient 1) or 100 mg (patient 2) of ZDV, and again on at least one occasion during chronic therapy (100 mg every 8 h). Concentrations of ZDV and its glucuronide metabolite (GZDV) were measured by radioimmunoassay.