Pharmacokinetics of zidovudine (azidothymidine). II. Development of metabolic and renal clearance pathways in the neonate.
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 less than 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.
Lopez-Anaya
A
A
Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle 98195.
Unadkat
J D
JD
Schumann
L A
LA
Smith
A L
AL
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D005965:Glucuronates / Q000097:blood; D014453:Glucuronosyltransferase / Q000097:blood; D006801:Humans; D008254:Macaca nemestrina; D008297:Male; D008657:Metabolic Clearance Rate; D015215:Zidovudine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D005965:Glucuronates; D015215:Zidovudine; D014453:Glucuronosyltransferase