PMID- 2136036
OWN - NLM
STAT- MEDLINE
DCOM- 19920820
LR  - 20191022
IS  - 0890-6238 (Print)
IS  - 0890-6238 (Linking)
VI  - 4
IP  - 3
DP  - 1990
TI  - Developmental toxicity and pharmacokinetics of oral and intravenous phenytoin in 
      the rat.
PG  - 191-202
AB  - Correlations between oral and intravenous (i.v.) doses of phenytoin, maternal 
      plasma levels, and subsequent developmental toxicity were examined in the 
      Sprague-Dawley rat. Oral administration of 150 to 1500 mg/kg and i.v. 
      administration of 25 to 100 mg/kg phenytoin from gestational days (GD) 8 to 17 
      resulted in a dose-dependent increase in maternal death and toxicity [impaired 
      motor function, decreased maternal weight gain (oral dose only)], 
      embryolethality, and intrauterine growth retardation, in addition to significant 
      increases in craniofacial (1125 mg/kg oral; 75 mg/kg i.v.) and urogenital (1125 
      mg/kg oral) malformations. Pharmacokinetic sampling in oral and i.v. groups on GD 
      8-9 and 16-17 revealed significant increases in maternal drug exposure over the 
      treatment period, as evidenced by 2- to 3-fold increases in total plasma 
      phenytoin (bound + free) half-life, area under the concentration curve, peak 
      concentration (oral dose only), and decreases in clearance. These findings 
      emphasize the importance of pharmacokinetics in the evaluation of 
      phenytoin-induced developmental toxicity.
FAU - Rowland, J R
AU  - Rowland JR
AD  - California Primate Research Center, University of California, Davis 95616.
FAU - Binkerd, P E
AU  - Binkerd PE
FAU - Hendrickx, A G
AU  - Hendrickx AG
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Reprod Toxicol
JT  - Reproductive toxicology (Elmsford, N.Y.)
JID - 8803591
RN  - 6158TKW0C5 (Phenytoin)
SB  - IM
MH  - Abnormalities, Drug-Induced/pathology
MH  - Administration, Oral
MH  - Animals
MH  - Body Weight/drug effects
MH  - Female
MH  - Fetal Resorption/chemically induced
MH  - Half-Life
MH  - Injections, Intravenous
MH  - Organ Size/drug effects
MH  - Phenytoin/pharmacokinetics/*toxicity
MH  - Pregnancy
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Reproduction/drug effects
EDAT- 1990/01/01 00:00
MHDA- 1990/01/01 00:01
CRDT- 1990/01/01 00:00
PHST- 1990/01/01 00:00 [pubmed]
PHST- 1990/01/01 00:01 [medline]
PHST- 1990/01/01 00:00 [entrez]
AID - 10.1016/0890-6238(90)90058-4 [doi]
PST - ppublish
SO  - Reprod Toxicol. 1990;4(3):191-202. doi: 10.1016/0890-6238(90)90058-4.