Additional investigation on the potentiation of phenytoin teratogenicity by fluconazole. 2003

Gian Mario Tiboni, and Franca Giampietro, and Stefania Angelucci, and Pasquale Moio, and Umberto Bellati, and Carmine Di Ilio
Sezione di Ostetricia e Ginecologia, Dipartimento di Medicina e Scienze dell'Invecchiamento, Facoltà di Medicina e Chirurgia, Università, Ospedale Via dei Vestini, 66013 Chieti, Italy. tiboni@unich.it

Fluconazole (FCZ) is a potent inhibitor of the cytochrome P450 (CYP)-mediated metabolism of the anti-epileptic agent phenytoin (PHT), a well-known human and animal teratogen. It has been postulated that phenytoin must be bioactivated via the CYP system to initiate teratogenesis. In contrast with this view, FCZ pretreatment has been previously shown to result in a potentiation of PHT teratogenesis. The current study was initiated to determine the impact of FCZ pretreatment on PHT exposure levels in maternal and embryonal compartments. HPLC analysis revealed that under a co-dosing FCZ-PHT regimen resulting in enhanced PHT teratogenesis, statistically significant higher PHT levels are detectable in maternal plasma and embryonic tissue in comparison to controls. These results further argue against a role for CYP system in teratogenic bioactivation of PHT.

UI MeSH Term Description Entries
D007274 Injections, Intraperitoneal Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall. Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D008297 Male Males
D008431 Maternal-Fetal Exchange Exchange of substances between the maternal blood and the fetal blood at the PLACENTA via PLACENTAL CIRCULATION. The placental barrier excludes microbial or viral transmission. Transplacental Exposure,Exchange, Maternal-Fetal,Exposure, Transplacental,Maternal Fetal Exchange
D008813 Mice, Inbred ICR An inbred strain of mouse that is used as a general purpose research strain, for therapeutic drug testing, and for the genetic analysis of CARCINOGEN-induced COLON CANCER. Mice, Inbred ICRC,Mice, ICR,Mouse, ICR,Mouse, Inbred ICR,Mouse, Inbred ICRC,ICR Mice,ICR Mice, Inbred,ICR Mouse,ICR Mouse, Inbred,ICRC Mice, Inbred,ICRC Mouse, Inbred,Inbred ICR Mice,Inbred ICR Mouse,Inbred ICRC Mice,Inbred ICRC Mouse
D010672 Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. Diphenylhydantoin,Fenitoin,Phenhydan,5,5-Diphenylhydantoin,5,5-diphenylimidazolidine-2,4-dione,Antisacer,Difenin,Dihydan,Dilantin,Epamin,Epanutin,Hydantol,Phenytoin Sodium,Sodium Diphenylhydantoinate,Diphenylhydantoinate, Sodium
D010920 Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (CHORIONIC VILLI) derived from TROPHOBLASTS and a maternal portion (DECIDUA) derived from the uterine ENDOMETRIUM. The placenta produces an array of steroid, protein and peptide hormones (PLACENTAL HORMONES). Placentoma, Normal,Placentome,Placentas,Placentomes
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011297 Prenatal Exposure Delayed Effects The consequences of exposing the FETUS in utero to certain factors, such as NUTRITION PHYSIOLOGICAL PHENOMENA; PHYSIOLOGICAL STRESS; DRUGS; RADIATION; and other physical or chemical factors. These consequences are observed later in the offspring after BIRTH. Delayed Effects, Prenatal Exposure,Late Effects, Prenatal Exposure
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D002972 Cleft Palate Congenital fissure of the soft and/or hard palate, due to faulty fusion. Cleft Palate, Isolated,Cleft Palates,Palate, Cleft,Palates, Cleft

Related Publications

Gian Mario Tiboni, and Franca Giampietro, and Stefania Angelucci, and Pasquale Moio, and Umberto Bellati, and Carmine Di Ilio
February 1986, Teratology,
Gian Mario Tiboni, and Franca Giampietro, and Stefania Angelucci, and Pasquale Moio, and Umberto Bellati, and Carmine Di Ilio
August 1998, Prenatal diagnosis,
Gian Mario Tiboni, and Franca Giampietro, and Stefania Angelucci, and Pasquale Moio, and Umberto Bellati, and Carmine Di Ilio
March 2012, Prescrire international,
Gian Mario Tiboni, and Franca Giampietro, and Stefania Angelucci, and Pasquale Moio, and Umberto Bellati, and Carmine Di Ilio
September 1996, The Pediatric infectious disease journal,
Gian Mario Tiboni, and Franca Giampietro, and Stefania Angelucci, and Pasquale Moio, and Umberto Bellati, and Carmine Di Ilio
January 1983, Progress in clinical and biological research,
Gian Mario Tiboni, and Franca Giampietro, and Stefania Angelucci, and Pasquale Moio, and Umberto Bellati, and Carmine Di Ilio
November 1989, The Medical journal of Australia,
Gian Mario Tiboni, and Franca Giampietro, and Stefania Angelucci, and Pasquale Moio, and Umberto Bellati, and Carmine Di Ilio
January 1973, Lancet (London, England),
Gian Mario Tiboni, and Franca Giampietro, and Stefania Angelucci, and Pasquale Moio, and Umberto Bellati, and Carmine Di Ilio
April 1991, Clinical pharmacology and therapeutics,
Gian Mario Tiboni, and Franca Giampietro, and Stefania Angelucci, and Pasquale Moio, and Umberto Bellati, and Carmine Di Ilio
December 1990, DICP : the annals of pharmacotherapy,
Gian Mario Tiboni, and Franca Giampietro, and Stefania Angelucci, and Pasquale Moio, and Umberto Bellati, and Carmine Di Ilio
March 1993, The American journal of the medical sciences,
Copied contents to your clipboard!