Influence of gestational diabetes mellitus on the stereoselective kinetic disposition and metabolism of labetalol in hypertensive patients

Abstract

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.

Concentration of tacrolimus and major metabolites in kidney transplant recipients as a function of diabetes mellitus and cytochrome P450 3A gene polymorphism

“…Carvalho et al (2011) have observed significantly lower glucuronidation capacity and exposure of labetalol, a UGT2B7 and 1A1 substrate, in women with gestational diabetes. Currently, the effect of diabetes on the expression and activity of UGT1A4 is unknown.…”

Pharmacological management of hypertension in pregnancy

“…9 The AUC for (RR)-labetalol (45.6; CI 40.3–74.4 ng•h/mL) is roughly half that for (SR)-labetalol (84.2; CI 63.8–119 ng•h/mL). 9 Stereoselective glucuronidation of orally administered drug results in more rapid clearance of the β-active isomer compared to the α-active isomer limiting the impact of oral labetalol on maternal heart rate – particularly at lower doses. Clinically, the pharmacokinetics of labetalol can be used to inform dosing in pregnancy.…”

“…9 When administered orally in pregnancy the apparent oral clearance of (RR)-labetalol (4.4; CI 36–7.4 L/h/kg) is higher than for (SR)-labetalol (2.9; CI 2.0–4.9 L/h/kg). 9 The AUC for (RR)-labetalol (45.6; CI 40.3–74.4 ng•h/mL) is roughly half that for (SR)-labetalol (84.2; CI 63.8–119 ng•h/mL). 9 Stereoselective glucuronidation of orally administered drug results in more rapid clearance of the β-active isomer compared to the α-active isomer limiting the impact of oral labetalol on maternal heart rate – particularly at lower doses.…”

“…((SS)-labetalol and (RS)-labetalol have little activity.) 9 When administered intravenously the pharmacokinetics are not stereoselective; the β-blocking isomer (RR)-labetalol and the α 1 -blocking isomer (SR)-labetalol are cleared at the same rate. 9 When administered orally in pregnancy the apparent oral clearance of (RR)-labetalol (4.4; CI 36–7.4 L/h/kg) is higher than for (SR)-labetalol (2.9; CI 2.0–4.9 L/h/kg).…”

“…9 When administered intravenously the pharmacokinetics are not stereoselective; the β-blocking isomer (RR)-labetalol and the α 1 -blocking isomer (SR)-labetalol are cleared at the same rate. 9 When administered orally in pregnancy the apparent oral clearance of (RR)-labetalol (4.4; CI 36–7.4 L/h/kg) is higher than for (SR)-labetalol (2.9; CI 2.0–4.9 L/h/kg). 9 The AUC for (RR)-labetalol (45.6; CI 40.3–74.4 ng•h/mL) is roughly half that for (SR)-labetalol (84.2; CI 63.8–119 ng•h/mL).…”