title: Sex differences in methamphetamine pharmacokinetics in adult rats and its transfer to pups through the placental membrane and breast milk.
abstract: BACKGROUND
  Methamphetamine (METH) abuse is a growing health problem worldwide, and METH use during pregnancy not only endangers the mother's health but also the developing fetus. To provide better insight into these risks, we performed the following experiments.
  
  
  METHODS
  First, we investigated how sex influences the pharmacokinetics of METH and amphetamine (AMP) in male and female rats. Subsequently, we simulated chronic exposure of prenatal infants to METH abuse by investigating brain and plasma levels of METH and AMP in dams and pups. Finally, we modeled chronic exposure of infants to METH via breast milk and investigated sex differences in pups with regard to drug levels and possible sensitization effect of chronic prenatal METH co-treatment.
  
  
  RESULTS
  We observed significantly higher levels of METH and AMP in the plasma and brain of female rats compared to males. Additionally, brain concentrations of METH and AMP in pups exposed to METH prenatally were equivalent to 62.13% and 37.78% relative to dam, respectively. Plasma concentrations of AMP where equivalent to 100% of the concentration in dams, while METH was equivalent to only 36.98%. Finally, we did not observe a significant effect relative to sex with regard to METH/AMP levels or sensitization effects linked to prenatal METH exposure.
  
  
  CONCLUSIONS
  We demonstrated that female rats display higher levels of METH and AMP, thus indicating a greater risk of addiction and toxicity. Furthermore, our data show that pups are exposed to both METH and AMP following dam exposure.
authors.affiliation: Institute of Chemical Technology, Technicka 5, Prague 166 28, Czech Republic; Institute of Physiology AS CR v.v.i., Videnska 1083, Prague 142 20, Czech Republic. Electronic address: rambousek@biomed.cas.cz.
authors.forename: Lukas
authors.initials: L
authors.lastname: Rambousek
authors.affiliation: Institute of Chemical Technology, Technicka 5, Prague 166 28, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Kacer
authors.affiliation: Institute of Chemical Technology, Technicka 5, Prague 166 28, Czech Republic.
authors.forename: Kamila
authors.initials: K
authors.lastname: Syslova
authors.affiliation: Institute of Chemical Technology, Technicka 5, Prague 166 28, Czech Republic.
authors.forename: Jakub
authors.initials: J
authors.lastname: Bumba
authors.affiliation: Prague Psychiatric Center, Ustavni 91/7, Prague 181 00, Czech Republic.
authors.forename: Vera
authors.initials: V
authors.lastname: Bubenikova-Valesova
authors.affiliation: Charles University in Prague, Third Faculty of Medicine, Department of Normal, Pathological and Clinical Physiology, Ke Karlovu 4, 120 00 Prague, Czech Republic.
authors.forename: Romana
authors.initials: R
authors.lastname: Slamberova
mesh_terms: D000661:Amphetamine / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D001923:Brain Chemistry; D000697:Central Nervous System Stimulants / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D008297:Male; D008694:Methamphetamine / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D008892:Milk / Q000737:chemistry*; D010920:Placenta / Q000737:chemistry; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D000661:Amphetamine
keywords: Amphetamine; Breast feeding milk; Mass spectrometry.; Methamphetamine; Pharmacokinetics; Sex differences