Biomedical subjects

S C Piscitelli

Publications and source records attributed to S C Piscitelli.

75 records · Page 5Linked to original sources

PubMedDate not supplied

Pharmacokinetics and pharmacodynamics of subcutaneous interleukin-2 in HIV-infected patients.

STUDY OBJECTIVES: To assess the pharmacokinetics and pharmacodynamics of subcutaneously administered interleukin-2 (IL-2) in patients infected with the human immunodeficiency virus (HIV). DESIGN: Open, dose-escalating phase I clinical trial. SETTING: Government research hospital. PATIENTS: Eighteen patients infected with HIV. INTERVENTIONS: Recombinant IL-2 at dosages of 12, 15, or 18 MIU/day was administered subcutaneously once or twice/day for 5 consecutive days every 2 months. A total of 28 cycles of therapy were included in the analysis. MEASUREMENTS AND MAIN RESULTS: Concentrations of IL-2 in serum were determined by a commercial enzyme-linked immunosorbent assay. Interleukin-2 was well absorbed, with peak concentrations from 21.9-112.9 IU/ml. Absorption was slow, with mean (+/- SD) time to maximum of 4.4 +/- 1.8 hours and a lag time of 26.9 +/- 13.7 minutes. Elimination half-life was 3.3 +/- 0.9 hours. The concentrations had wide variability both within and among patients. Levels of tumor necrosis factor-alpha were increased. Maximum body temperature and systemic side effects were associated with peak serum levels. CONCLUSION: Interleukin-2 is well absorbed after subcutaneous injection in HIV-infected patients, and that route of administration is an alternative to intravenous infusions.

Adult↗

PubMedDate not supplied

Pharmacometric analysis of the effect of furosemide on suramin pharmacokinetics.

STUDY OBJECTIVE: To characterize the effects of furosemide on the pharmacokinetics of suramin, a renally eliminated investigational antineoplastic agent. DESIGN: Retrospective population pharmacokinetic analysis. SETTING: Government biomedical research facility. PATIENTS: Twenty-six men with hormone-refractory prostate cancer and one with adrenocortical carcinoma. INTERVENTIONS: Patients received suramin by continuous or intermittent infusion with and without concomitant furosemide. MEASUREMENTS AND MAIN RESULTS: Optimum suramin regimens were achieved by adaptive feedback control, and pharmacokinetic data were collected both in the presence and absence of furosemide. Suramin concentrations were determined by high-performance liquid chromatography (coefficient of variation < 8%). Suramin concentrations were fit to a three-compartment linear model with six coefficients and two rate inputs, which allowed furosemide to affect suramin pharmacokinetics. Individual and population parameter estimates were determined using the iterative two-stage approach. Concomitant furosemide was associated with a median decrease in total body clearance of suramin by 36% (range 0-63%, p < 0.0001). No other parameter was significantly altered, and there was no trend for change in any pharmacokinetic value with time. Suramin plasma concentrations were simulated with and without prolonged furosemide therapy in 26 patients for 12 weeks. The average suramin concentration increased by greater than 33% in 12 patients; 2 patients had a greater than 67% increase in this extreme case model. CONCLUSION: Coadministration of furosemide with suramin can cause an increase in suramin concentrations; however, due to suramin's long half-life, its rate of accumulation is very slow. Nonetheless, in individuals receiving suramin by nonadaptive control, appropriate precautions should be taken when prolonged furosemide therapy is begun.

Adrenal Cortex Neoplasms↗

PubMedDate not supplied

Alteration in indinavir clearance during interleukin-2 infusions in patients infected with the human immunodeficiency virus.

STUDY OBJECTIVE: To evaluate the effect of interleukin-2 (IL-2) infusions on the pharmacokinetics of indinavir in patients infected with the human immunodeficiency virus. DESIGN: Observational, noncontrolled trial and prospective, open-label, nonrandomized, pharmacokinetic study. SETTING: Government research hospital. PATIENTS: Seventeen patients receiving indinavir 800 mg every 8 hours and a 5-day continuous infusion of recombinant IL-2. INTERVENTIONS: Observational study: trough indinavir concentrations were measured on day 1 and day 5 of IL-2 as part of a clinical trial. Prospective study: serial plasma samples were collected on days 1 and 5 of IL-2 to determine indinavir concentrations. Samples were also collected over the study period to determine IL-6 concentrations. The data were fit by a one-compartment model that allowed clearance to change based on IL-6 production and by standard noncompartmental equations. MEASUREMENTS AND MAIN RESULTS: The area under the curve of indinavir increased in eight of nine patients by a mean of 88% (range -29-215%) between days 1 and 5 of IL-2 infusion. Over this period, IL-6 concentrations also increased in all patients and indinavir clearance significantly decreased. Observational data in eight patients from the clinical trial showed significantly increased indinavir trough concentrations from 264+/-493 to 670+/-677 ng/ml in the presence of IL-2. CONCLUSION: Indinavir concentrations were altered during IL-2 infusions, possibly by induction of IL-6. Investigation into the effects of other proinflammatory cytokines is warranted.

Adult↗