Pharmacokinetics of zidovudine (azidothymidine) . II. Development of metabolic and renal clearance pathways in the neonate
Lopez-Anaya, A.; Unadkat, J.D.; Schumann, L.A.; Smith, A.L.
Journal of Acquired Immune Deficiency Syndromes 3(11): 1052-1058
1990
ISSN/ISBN: 0894-9255 PMID: 2120418 Document Number: 356455
The pharmacokinetics of zidovudine (ZDV or azidothymidine) were investigated in newborn macaques (Macaca nemestrina) at various ages ranging from less than 1 week to 4 months. The mean ZDV total plasma clearance, renal clearance, and the metabolic clearance of ZDV to the glucuronide (ZDVG) were significantly (p < 0.05) smaller during the first week of life (6.15 .+-. 1.03, 4.25 .+-. 0.36, and 1.19 .+-. 0.67 ml/min/kg, respectively) than the corresponding estimates at the age of 4 months (19.62 .+-. 3.5, 8.28 .+-. 1.90, and 8.28 .+-. 2.24 ml/min/kg, respectively). The mean estimates of these parameters at 4 months were close to those found in adult macaques (23.55 .+-. 1.48, 10.05 .+-. 0.75, and 10.5 .+-. 1.9 ml/min/kg, respectively), indicating that these clearance pathways develop rapidly, within 4 months of birth. If similar results are obtained in human neonates, therapeutic drug monitoring should be instituted when administering ZDV to this population so that the dose of ZDV may be adjusted to correspond with age-related changes in total plasma clearance of ZDV.