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Population Pharmacokinetics and Pharmacodynamics of Zidovudine in HIV‐Infected Infants and Children
Author(s) -
Capparelli Edmund V.,
Englund Janet A.,
Connor James D.,
Spector Stephen A.,
McKinney Ross E.,
Palumbo Paul,
Baker Carol J.
Publication year - 2003
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270002239821
Subject(s) - zidovudine , medicine , pharmacokinetics , didanosine , pharmacodynamics , population , anemia , pharmacology , pediatrics , human immunodeficiency virus (hiv) , immunology , viral disease , environmental health
The purpose of this study was to assess the population pharmacokinetics (PK) and pharmacodynamics (PD) of zidovudine (ZDV) in infants and children. This evaluation includes 394 subjects who participated in Pediatric AIDS Clinical Trials Group (PACTG) Study 152 and received either ZDV alone or in combination with didanosine. The most significant PK covariate was age, with infants < 2 years of age having reduced size‐adjusted clearance. ZDV exposure was weakly related to maximal reduction in immune complex‐dissociated (ICD) p24 antigen but not to reduction at 6 months. Mild chronic anemia occurred in 7.6% of subjects with ZDV average concentration < 1.3 μM (350 ng/mL) versus in 23.4% subjects with higher ZDV concentrations ( p < 0.001). There was a direct linear relationship between hemoglobin and ZDV levels. It was concluded that ZDV oral clearance is reduced in infants compared to older children. This lower clearance leads to higher ZDV exposure in infants and contributes to increased hematologic toxicity.