Inger Öhman

Lamotrigine in Pregnancy: Pharmacokinetics During Delivery, in the Neonate, and During Lactation

Summary: Purpose: To investigate the pharmacokinetics of lamotrigine (LTG) during delivery, during the neonatal period, and lactation.

Oral contraceptives reduce lamotrigine plasma levels

The mean steady-state plasma concentration of lamotrigine (LTG) was 13 μmol/L in 22 women taking LTG in combination oral contraceptives (OC) compared with 28 μmol/L among 30 women on LTG who did not take OC (p < 0.0001). The LTG dose/body weight/plasma concentration was 2.1 L/kg/day in women on OC compared with 0.8 L/kg/day in women without OC (p < 0.0001), indicating that LTG plasma levels are reduced by >50% during OC co-medication. It is advisable to monitor LTG plasma levels in conjunction with initiation or withdrawal of OC in women on LTG therapy.

Pharmacokinetics of levetiracetam during pregnancy, delivery, in the neonatal period, and lactation

Summary:  Purpose: To study pharmacokinetics of levetiracetam (LEV) during pregnancy, delivery, lactation, and in the neonatal period.

Lamotrigine in Pregnancy and Lactation: A case Report

Summary: Purpose: We investigated the effect of pregnancy on the kinetics of lamotrigine (LTG), passage of LTG over the placenta and the excretion of the drug in breast milk.

Topiramate kinetics during delivery, lactation, and in the neonate : Preliminary observations

Summary:  Purpose: To study the pharmacokinetics of topiramate (TPM) during delivery, lactation, and in the neonate.

Oral contraceptives induce lamotrigine metabolism: Evidence from a double-blind placebo-controlled trial.

Summary:  Purpose: This study evaluates the effect of oral contraceptives on lamotrigine (LTG) plasma concentrations and urine excretion of LTG metabolites in a double‐blind, placebo‐controlled, crossover study in patients with epilepsy.

Pharmacokinetics of Gabapentin during Delivery, in the Neonatal Period, and Lactation: Does a Fetal Accumulation Occur during Pregnancy?

Summary:  Purpose: To study the pharmacokinetics of gabapentin (GBP) during delivery, lactation, and in the neonatal period.

Plasma concentrations of lamotrigine and its 2-N-glucuronide metabolite during pregnancy in women with epilepsy

Objective: To further characterize pregnancy‐induced alterations in the pharmacokinetics of lamotrigine (LTG).

Effects of pregnancy and contraception on lamotrigine disposition: New insights through analysis of lamotrigine metabolites

OBJECTIVE To investigate possible underlying mechanisms for alterations in lamotrigine (LTG) kinetics by gestation and use of contraceptives. METHODS Plasma concentrations of LTG and its main metabolite lamotrigine-2-N-glucuronide (2-N-GLUC) were measured in 31 women on LTG taking combined oral contraceptives (COC), in 12 with contraceptive intrauterine devices containing levonorgestrel (CIUD), and in 20 on LTG without hormonal contraception (controls). We also measured the levels of LTG and 2-N-GLUC in plasma and urine in eight women during pregnancy, and up to three months postpartum. LTG levels in plasma were measured by high-performance liquid chromatography method (HPLC) and N-2-GLUC in urine and plasma and LTG in urine by liquid chromatography-mass spectrometry (LC/MS). RESULTS There were no significant differences in LTG dose/concentration (D/C), or N-2-GLUC/LTG ratios between women with CIUD and controls. In contrast, compared to controls, the LTG D/C ratio was 56% higher in women taking COC (mean+/-SD, 83+/-47 versus 53.0+/-24.2; p<0.01) and N-2-GLUC/LTG ratio 82% higher in women taking COC (mean 0.477+/-0.212 SD versus 0.262+/-0.127; p<0.0003. The 2-GLUC/LTG ratios were 154% higher in plasma and 122% higher in urine in late pregnancy compared with baseline 3months postpartum. CONCLUSIONS Our data indicate that the alterations in LTG kinetics in pregnancy as well as those induced by COC are mainly explained by enzymatic induction of the N-2-glucuronide pathway. In addition we found no evidence for an interaction between LTG and CIUD.

Determination of lamotrigine and its metabolites in human plasma by liquid chromatography-mass spectrometry.

A method based on electrospray ionization liquid chromatography-mass spectrometry was developed for the quantitative determination of lamotrigine and three of its reported metabolites, lamotrigine-2-N-glucuronide, lamotrigine-2-N-methyl, and lamotrigine-2-N-oxide in human blood plasma. The method utilized sample preparation by precipitation of proteins with acetonitrile, chromatographic separation on a reversed-phase system by gradient elution, and monitoring of the protonated molecular ions. Two internal standards, 3,5-diamino-6-(2-methoxyphenyl)-1,2,4-triazine and morphine-3-glucuronide-D3, were utilized to achieve precise quantification. The method validation comprised a demonstration of an agreement in the quantification of lamotrigine with that of a routine HPLC-UV method. The limits of detection were between 0.05 and 0.16 μmol/L. The method was employed for the measurement of clinical samples collected from 55 patients in steady-state prior to the dose intake (trough level). Lamotrigine and the 2-N-glucuronide were typically detected, while the N-methyl and N-oxide metabolites were detected only rarely. The median lamotrigine plasma level was 24.0 μmol/L (range, 4.3 to 64 μmol/L), the median 2-N-glucuronide level was 2.4 μmol/L (range, <0.05 to 24 μmol/L), and the median lamotrigine 2-N-glucuronide/lamotrigine ratio was 0.11 (range, <0.01 to 0.64). In conclusion, this liquid chromatographic-mass spectrometric method is suitable for simultaneous determination of lamotrigine and its metabolites in human plasma.