title: Influence of gestational diabetes mellitus on the stereoselective kinetic disposition and metabolism of labetalol in hypertensive patients.
abstract: OBJECTIVE
  This study investigated the influence of gestational diabetes mellitus on the kinetic disposition and stereoselective metabolism of labetalol administered intravenously or orally.
  
  
  METHODS
  Thirty hypertensive women during the last trimester of pregnancy were divided into four groups: non-diabetic and diabetic women treated with intravenous or oral labetalol.
  
  
  RESULTS
  The pharmacokinetics of labetalol was not stereoselective in diabetic or non-diabetic pregnant women receiving the drug intravenously. However, oral administration of labetalol resulted in lower values of the area under the plasma concentration versus time curve (AUC) for the β-blocker (RR) than for the other enantiomers in both diabetic and non-diabetic women. Gestational diabetes mellitus caused changes in the kinetic disposition of the labetalol stereoisomers when administered orally. The AUC values for the less potent adrenoceptor antagonist (SS) and for the α-blocking (SR) isomers were higher in diabetic than in non-diabetic pregnant women.
  
  
  CONCLUSIONS
  The approximately 100% higher AUC values obtained for the (SR) isomer in diabetic pregnant women treated with oral labetalol may be of clinical relevance in terms of the α-blocking activity of this isomer.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Teresa Maria J P
authors.initials: TM
authors.lastname: Carvalho
authors.forename: Ricardo de Carvalho
authors.initials: Rde C
authors.lastname: Cavalli
authors.forename: Sérgio P
authors.initials: SP
authors.lastname: Cunha
authors.forename: Cláudia O
authors.initials: CO
authors.lastname: de Baraldi
authors.forename: Maria P
authors.initials: MP
authors.lastname: Marques
authors.forename: Natalícia J
authors.initials: NJ
authors.lastname: Antunes
authors.forename: Ana Leonor P C
authors.initials: AL
authors.lastname: Godoy
authors.forename: Vera Lucia
authors.initials: VL
authors.lastname: Lanchote
mesh_terms: D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D000328:Adult; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D016640:Diabetes, Gestational / Q000378:metabolism*; D005260:Female; D020719:Glucuronides / Q000097:blood / Q000378:metabolism; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D007275:Injections, Intravenous; D007741:Labetalol / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D011247:Pregnancy; D013237:Stereoisomerism; D055815:Young Adult
chemical_list: D000319:Adrenergic beta-Antagonists; D020719:Glucuronides; D007741:Labetalol