PMID- 16767756
OWN - NLM
STAT- MEDLINE
DCOM- 20070612
LR  - 20131121
IS  - 1542-9733 (Print)
IS  - 1542-9733 (Linking)
VI  - 77
IP  - 3
DP  - 2006 Jun
TI  - Prenatal developmental toxicity evaluation of 2',3'-dideoxyinosine (ddI) and 
      2',3'-didehydro-3'-deoxythymidine (d4T) co-administered to Swiss Albino (CD-1) 
      mice.
PG  - 207-15
AB  - BACKGROUND: In pregnant women, antiretroviral drugs improve maternal health and 
      reduce vertical transmission of human immunodeficiency virus to the infant. 
      However, few nonclinical studies have examined the potential for adverse drug 
      interactions. METHODS: On gestational days (GD) 6-16, mice were dosed with 
      vehicle, ddI (360, 1440, or 2,880 mg/kg/day, p.o.), d4T (60, 240, or 480), or 
      ddI/d4T combinations (360/60, 1,440/240, or 2,880/480). Daily doses were divided 
      into two equal parts that were administered >or=6-hr apart. Body weight, clinical 
      signs, and feed consumption were monitored. Pregnancies (22-24/group) were 
      confirmed at necropsy. Maternal liver and gravid uterine weights (GUW), uterine 
      implants (resorption, live or dead fetus), fetal body weight, gender, and 
      morphologic anomalies (external, visceral, skeletal) were recorded. RESULTS: 
      Maternal body weight, clinical signs, and GUW were unaffected. Maternal weight 
      change corrected for GUW was greater than controls at 60 and 480 d4T. Relative 
      feed consumption during treatment was increased relative to controls at 1,440 and 
      2,880 ddI and 2,880/480 ddI/d4T. Relative maternal liver weight was elevated 
      above controls at 240 and 480 d4T and 2,880/480 ddI/d4T, and above the 
      constituent dose of ddI at 1,440/240 and 2,880/480 ddI/d4T. Liver weight was not 
      affected by ddI and there was no significant drug interaction. Prenatal mortality 
      and morphologic anomalies were not increased. Fetal body weight showed only a 
      decreasing trend for ddI/d4T, no effect for ddI or d4T, and no statistically 
      significant drug interaction. CONCLUSIONS: In pregnant mice, ddI/d4T combinations 
      were not associated with well-defined developmental toxicity or adverse drug 
      interactions.
FAU - Price, Catherine J
AU  - Price CJ
AD  - Life Sciences and Toxicology, RTI International, Research Triangle Park, North 
      Carolina 27709-2194, USA. cjp@rti.org
FAU - George, Julia D
AU  - George JD
FAU - Marr, Melissa C
AU  - Marr MC
FAU - Myers, Christina B
AU  - Myers CB
FAU - Bieler, Gayle S
AU  - Bieler GS
FAU - Williams, Rick L
AU  - Williams RL
FAU - Jahnke, Gloria D
AU  - Jahnke GD
LA  - eng
GR  - N01-ES-65405/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Birth Defects Res B Dev Reprod Toxicol
JT  - Birth defects research. Part B, Developmental and reproductive toxicology
JID - 101155115
RN  - BO9LE4QFZF (Stavudine)
RN  - K3GDH6OH08 (Didanosine)
SB  - IM
MH  - Animals
MH  - Animals, Outbred Strains
MH  - Didanosine/*administration & dosage/*toxicity
MH  - Embryo Implantation/drug effects
MH  - Feeding Behavior/drug effects
MH  - Female
MH  - Fetal Death
MH  - Fetal Weight/drug effects
MH  - Fetus/abnormalities/*drug effects/*embryology
MH  - Litter Size/drug effects
MH  - Mice
MH  - Organ Size/drug effects
MH  - Pregnancy
MH  - Stavudine/*administration & dosage/*toxicity
EDAT- 2006/06/13 09:00
MHDA- 2007/06/15 09:00
CRDT- 2006/06/13 09:00
PHST- 2006/06/13 09:00 [pubmed]
PHST- 2007/06/15 09:00 [medline]
PHST- 2006/06/13 09:00 [entrez]
AID - 10.1002/bdrb.20076 [doi]
PST - ppublish
SO  - Birth Defects Res B Dev Reprod Toxicol. 2006 Jun;77(3):207-15. doi: 
      10.1002/bdrb.20076.