Pre- and postnatal treatment of the rhesus macaque (Macaca mulatta) with azidothymidine

I. Fetal studies

Alice F Tarantal, R. J. Spanggord, Andrew G Hendrickx

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Methods for treating noninfected macaque fetuses with azidothymidine (AZT) in utero were studied in order to determine the potential for toxicity during prenatal life. Multiple routes were investigated including direct fetal treatment [intraamniotic (n = 4) or intraperitoneal (IP) (n = 14) every 10 days, gestational day (GD) 60-160; 20 mg/kg] and maternal treatment [oral 60 mg/kg/day divided every 8 h (n = 4) or via subcutaneous (SQ) osmotic pumps (Alzet®), 1.4 mg/kg/h (n = 4) or 1.1 mg/kg/h (n = 10); GD 60-160]. Ten vehicle controls were included. Prenatal growth was monitored sonographically and fetal (amniotic fluid and blood) and maternal (blood and urine) samples were collected periodically to monitor drug levels and hematologic status. Results indicated an increased incidence of abortion, fetal/neonatal death, and premature delivery in all AZT-treated groups with minimal effects (1 abortion, 1 premature delivery) at 1.1 mg/kg/h SQ. Statistically significant effects on maternal and fetal red cell counts, hemoglobins, and hematocrits were observed with maternal oral and SQ administration but not direct fetal treatment. Drug levels in maternal (pumps: 0.13 ± 0.02 μg/ml; oral: 0.79 ± 0.08) and fetal plasma (pumps: 0.17 ± 0.02 μg/ml; oral: 1.02 ± 0.16) were similar during the course of gestation, with no indication of drug accumulation over time. All neonates were grossly normal at delivery with no significant effects on Apgar scores or overall body size. Chronic treatment via the maternal SQ (pump) route at the lowest dose studied was determined to be the most efficient; continuous and consistent drug levels were achieved in both the fetus and dam throughout gestation, although prenatal hematologic toxicity was observed.

Original languageEnglish (US)
Pages (from-to)10-19
Number of pages10
JournalPediatric AIDS and HIV Infection
Volume5
Issue number1
StatePublished - 1994

Fingerprint

Zidovudine
Macaca mulatta
Mothers
Pharmaceutical Preparations
Fetus
Therapeutics
Pregnancy
Fetal Death
Apgar Score
Macaca
Body Size
Amniotic Fluid
Hematocrit
Oral Administration
Hemoglobins
Cell Count
Urine
Incidence
Growth

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Pre- and postnatal treatment of the rhesus macaque (Macaca mulatta) with azidothymidine : I. Fetal studies. / Tarantal, Alice F; Spanggord, R. J.; Hendrickx, Andrew G.

In: Pediatric AIDS and HIV Infection, Vol. 5, No. 1, 1994, p. 10-19.

Research output: Contribution to journalArticle

@article{d8c60456c3a044a297e156a3a467ea12,
title = "Pre- and postnatal treatment of the rhesus macaque (Macaca mulatta) with azidothymidine: I. Fetal studies",
abstract = "Methods for treating noninfected macaque fetuses with azidothymidine (AZT) in utero were studied in order to determine the potential for toxicity during prenatal life. Multiple routes were investigated including direct fetal treatment [intraamniotic (n = 4) or intraperitoneal (IP) (n = 14) every 10 days, gestational day (GD) 60-160; 20 mg/kg] and maternal treatment [oral 60 mg/kg/day divided every 8 h (n = 4) or via subcutaneous (SQ) osmotic pumps (Alzet{\circledR}), 1.4 mg/kg/h (n = 4) or 1.1 mg/kg/h (n = 10); GD 60-160]. Ten vehicle controls were included. Prenatal growth was monitored sonographically and fetal (amniotic fluid and blood) and maternal (blood and urine) samples were collected periodically to monitor drug levels and hematologic status. Results indicated an increased incidence of abortion, fetal/neonatal death, and premature delivery in all AZT-treated groups with minimal effects (1 abortion, 1 premature delivery) at 1.1 mg/kg/h SQ. Statistically significant effects on maternal and fetal red cell counts, hemoglobins, and hematocrits were observed with maternal oral and SQ administration but not direct fetal treatment. Drug levels in maternal (pumps: 0.13 ± 0.02 μg/ml; oral: 0.79 ± 0.08) and fetal plasma (pumps: 0.17 ± 0.02 μg/ml; oral: 1.02 ± 0.16) were similar during the course of gestation, with no indication of drug accumulation over time. All neonates were grossly normal at delivery with no significant effects on Apgar scores or overall body size. Chronic treatment via the maternal SQ (pump) route at the lowest dose studied was determined to be the most efficient; continuous and consistent drug levels were achieved in both the fetus and dam throughout gestation, although prenatal hematologic toxicity was observed.",
author = "Tarantal, {Alice F} and Spanggord, {R. J.} and Hendrickx, {Andrew G}",
year = "1994",
language = "English (US)",
volume = "5",
pages = "10--19",
journal = "Pediatric AIDS and HIV Infection",
issn = "1045-5418",
publisher = "Mary Ann Liebert Inc.",
number = "1",

}

TY - JOUR

T1 - Pre- and postnatal treatment of the rhesus macaque (Macaca mulatta) with azidothymidine

T2 - I. Fetal studies

AU - Tarantal, Alice F

AU - Spanggord, R. J.

AU - Hendrickx, Andrew G

PY - 1994

Y1 - 1994

N2 - Methods for treating noninfected macaque fetuses with azidothymidine (AZT) in utero were studied in order to determine the potential for toxicity during prenatal life. Multiple routes were investigated including direct fetal treatment [intraamniotic (n = 4) or intraperitoneal (IP) (n = 14) every 10 days, gestational day (GD) 60-160; 20 mg/kg] and maternal treatment [oral 60 mg/kg/day divided every 8 h (n = 4) or via subcutaneous (SQ) osmotic pumps (Alzet®), 1.4 mg/kg/h (n = 4) or 1.1 mg/kg/h (n = 10); GD 60-160]. Ten vehicle controls were included. Prenatal growth was monitored sonographically and fetal (amniotic fluid and blood) and maternal (blood and urine) samples were collected periodically to monitor drug levels and hematologic status. Results indicated an increased incidence of abortion, fetal/neonatal death, and premature delivery in all AZT-treated groups with minimal effects (1 abortion, 1 premature delivery) at 1.1 mg/kg/h SQ. Statistically significant effects on maternal and fetal red cell counts, hemoglobins, and hematocrits were observed with maternal oral and SQ administration but not direct fetal treatment. Drug levels in maternal (pumps: 0.13 ± 0.02 μg/ml; oral: 0.79 ± 0.08) and fetal plasma (pumps: 0.17 ± 0.02 μg/ml; oral: 1.02 ± 0.16) were similar during the course of gestation, with no indication of drug accumulation over time. All neonates were grossly normal at delivery with no significant effects on Apgar scores or overall body size. Chronic treatment via the maternal SQ (pump) route at the lowest dose studied was determined to be the most efficient; continuous and consistent drug levels were achieved in both the fetus and dam throughout gestation, although prenatal hematologic toxicity was observed.

AB - Methods for treating noninfected macaque fetuses with azidothymidine (AZT) in utero were studied in order to determine the potential for toxicity during prenatal life. Multiple routes were investigated including direct fetal treatment [intraamniotic (n = 4) or intraperitoneal (IP) (n = 14) every 10 days, gestational day (GD) 60-160; 20 mg/kg] and maternal treatment [oral 60 mg/kg/day divided every 8 h (n = 4) or via subcutaneous (SQ) osmotic pumps (Alzet®), 1.4 mg/kg/h (n = 4) or 1.1 mg/kg/h (n = 10); GD 60-160]. Ten vehicle controls were included. Prenatal growth was monitored sonographically and fetal (amniotic fluid and blood) and maternal (blood and urine) samples were collected periodically to monitor drug levels and hematologic status. Results indicated an increased incidence of abortion, fetal/neonatal death, and premature delivery in all AZT-treated groups with minimal effects (1 abortion, 1 premature delivery) at 1.1 mg/kg/h SQ. Statistically significant effects on maternal and fetal red cell counts, hemoglobins, and hematocrits were observed with maternal oral and SQ administration but not direct fetal treatment. Drug levels in maternal (pumps: 0.13 ± 0.02 μg/ml; oral: 0.79 ± 0.08) and fetal plasma (pumps: 0.17 ± 0.02 μg/ml; oral: 1.02 ± 0.16) were similar during the course of gestation, with no indication of drug accumulation over time. All neonates were grossly normal at delivery with no significant effects on Apgar scores or overall body size. Chronic treatment via the maternal SQ (pump) route at the lowest dose studied was determined to be the most efficient; continuous and consistent drug levels were achieved in both the fetus and dam throughout gestation, although prenatal hematologic toxicity was observed.

UR - http://www.scopus.com/inward/record.url?scp=0028226810&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028226810&partnerID=8YFLogxK

M3 - Article

VL - 5

SP - 10

EP - 19

JO - Pediatric AIDS and HIV Infection

JF - Pediatric AIDS and HIV Infection

SN - 1045-5418

IS - 1

ER -