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A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses
Published on: August 31, 2014
Phase I evaluation of zalcitabine administered to human immunodeficiency virus-infected children
E G Chadwick1, L A Nazareno, T J Nieuwenhuis
1Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois, USA.
Insights
Zalcitabine (ddC) was safe and well-tolerated in HIV-infected children. Pharmacokinetic analysis showed rapid absorption and faster clearance in children compared to adults, suggesting dose adjustments may be needed.
Area of Science:
- Pediatric Pharmacology
- Infectious Diseases
- Pharmacokinetics
Background:
- Human immunodeficiency virus (HIV) infection impacts children globally.
- Antiretroviral therapies, including zalcitabine (ddC), are crucial for managing pediatric HIV.
- Understanding the pharmacokinetics of ddC in children is essential for optimizing treatment.
Purpose of the Study:
- To evaluate the safety and tolerability of a single oral dose of zalcitabine (ddC) in HIV-infected children.
- To characterize the pharmacokinetic profile of ddC in this pediatric population.
- To compare pediatric pharmacokinetics with existing adult data.
Main Methods:
- A single oral dose of zalcitabine (ddC) at 0.02 mg/kg was administered to 23 mildly symptomatic HIV-infected children.
- Blood samples were collected serially up to 8 hours post-dose.
- Plasma ddC concentrations were quantified using ion spray liquid chromatography/tandem mass spectrometry.
Main Results:
- Zalcitabine (ddC) was well-tolerated with no observed side effects.
- Rapid absorption was noted, with mean Tmax of 1 hour.
- Mean elimination half-life was 1.4 hours, with a mean total body clearance of 14.6 mL/min/kg.
- Observed plasma concentrations and half-life were lower than in adults, suggesting faster clearance in children.
Conclusions:
- Zalcitabine (ddC) demonstrates a favorable safety and tolerability profile in mildly symptomatic HIV-infected children.
- The pharmacokinetic profile in children suggests potentially more rapid elimination compared to adults.
- Further studies may be warranted to establish optimal dosing regimens for pediatric populations.
Abstract:
The safety, tolerability, and pharmacokinetics of zalcitabine (ddC) in a single oral dose (0.02 mg/kg) was evaluated in 23 mildly symptomatic human immunodeficiency virus-infected children (mean age, 4.2 years). After administration of ddC, blood samples were obtained at 0.5, 1, 1.5, 2, 4, 6, and 8 h for analysis. The drug was well tolerated and no side effects were noted. Plasma ddC levels were determined by ion spray liquid chromatography/tandem mass spectrometry. ddC was rapidly absorbed, with a mean maximum plasma concentration of 9.3 ng/mL (range, 3.2-14.1) attained within a mean of 1 h (range, 0.5-2.0). Mean elimination half-life was 1.4 h (range, 1.0-3.5), mean area under the plasma concentration-time curve was 25 ng.h/mL (range, 11-37), and mean total body clearance was 14.6 mL/min/kg (range, 8.9-30.6). Plasma concentrations were lower and the half-life shorter in these children than in adults given comparable doses, suggesting that ddC may be cleared more rapidly in children than adults.
