PMID- 10959545
OWN - NLM
STAT- MEDLINE
DCOM- 20001228
LR  - 20221207
IS  - 0148-0545 (Print)
IS  - 0148-0545 (Linking)
VI  - 23
IP  - 3
DP  - 2000 Aug
TI  - Impact of antenatal exposure of mice to fenfluramine on cardiac development and 
      long-term growth of the offspring.
PG  - 419-31
AB  - The objective of this investigation was to determine, in a placebo-controlled 
      manner, whether antenatal exposure to formulations of fenfluramine and 
      dexfenfluramine impacted cardiac development and long-term growth of exposed mice 
      offspring. One hundred forty-four CD-1 mice were randomized to six treatment 
      groups (n=23 or 25) to obtain, per group, 5 gravids for killing on gestational 
      day (GD) 15 and < or =10 deliveries for assessing growth of the offspring. Either 
      fenfluramine preparation was administered in feed bars in two doses: 1 and 3.2 
      times the equivalent human daily dosage according to body surface area. The drugs 
      were given from 2 weeks before mating until GD 15. The mice ingested each drug at 
      target values, averaging 10.5+/-0.3 and 31.8+/-1.9 mg/kg/d for fenfluramine and 
      5.0+/-0.2 and 16.2+/-0.4 mg/kg/d for dexfenfluramine. The drug concentration was 
      about 36% in the fetal brain compared with the adult brain. The maternal and the 
      offspring hearts, including mitral and aortic valves, of fenfluramine-exposed 
      mice were indistinguishable from the placebo-exposed mice. The duration of 
      gestation and the litter size were the same between the treatment groups. The 
      mean body weights, body lengths, and head circumferences and early functional 
      testing did not differ significantly between the fenfluramine or 
      dexfenfluramine-exposed offspring and the placebo-exposed offspring. There were 
      no significant treatment differences in growth measured as body weights to PND 
      120. Neither fenfluramine formulation, given before conception and during 
      gestation, impacted cardiac development and long-term growth of the mice 
      offspring.
FAU - Rayburn, W F
AU  - Rayburn WF
AD  - Department of Obstetrics and Gynecology, The University of Oklahoma Health 
      Sciences Center, Oklahoma City, USA. wrayburn@somasf.unm.edu
FAU - Sienko, A E
AU  - Sienko AE
FAU - Gonzalez, C L
AU  - Gonzalez CL
FAU - Christensen, H D
AU  - Christensen HD
FAU - Kupiec, T C
AU  - Kupiec TC
FAU - Paulsen, A L
AU  - Paulsen AL
FAU - Stewart, J D
AU  - Stewart JD
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Drug Chem Toxicol
JT  - Drug and chemical toxicology
JID - 7801723
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 2DS058H2CF (Fenfluramine)
RN  - E35R3G56OV (Dexfenfluramine)
SB  - IM
MH  - Abnormalities, Drug-Induced
MH  - Animals
MH  - Animals, Newborn/growth & development
MH  - Aortic Valve/anatomy & histology/drug effects
MH  - Body Weight/drug effects
MH  - Brain/drug effects/metabolism
MH  - Dexfenfluramine/pharmacokinetics/toxicity
MH  - Embryonic and Fetal Development/*drug effects
MH  - Female
MH  - Fenfluramine/pharmacokinetics/*toxicity
MH  - Fertility/drug effects
MH  - Heart/*drug effects/embryology/growth & development
MH  - Litter Size/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mitral Valve/anatomy & histology/drug effects
MH  - Pregnancy
MH  - Selective Serotonin Reuptake Inhibitors/pharmacokinetics/*toxicity
MH  - Tissue Distribution
EDAT- 2000/08/26 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/08/26 11:00
PHST- 2000/08/26 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/08/26 11:00 [entrez]
AID - 10.1081/dct-100100126 [doi]
PST - ppublish
SO  - Drug Chem Toxicol. 2000 Aug;23(3):419-31. doi: 10.1081/dct-100100126.