Influence of gestational diabetes mellitus on the stereoselective kinetic disposition and metabolism of labetalol in hypertensive patients.
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.
Carvalho
Teresa Maria J P
TM
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Cavalli
Ricardo de Carvalho
Rde C
Cunha
Sérgio P
SP
de Baraldi
Cláudia O
CO
Marques
Maria P
MP
Antunes
Natalícia J
NJ
Godoy
Ana Leonor P C
AL
Lanchote
Vera Lucia
VL
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
D000319:Adrenergic beta-Antagonists; D020719:Glucuronides; D007741:Labetalol