Lamotrigine and its N2-glucuronide during pregnancy : The significance of renal clearance and estradiol
(2011) In Epilepsy Research 94(3). p.198-205- Abstract
Purpose: To investigate the physiological mechanisms behind the pronounced decline of lamotrigine (LTG) serum concentrations during pregnancy. Methods: Serum and urine concentrations of LTG and its main metabolite, LTG-N2-glucuronide (LTG-GLUC), were measured monthly in 21 pregnancies of 19 women using LTG. Simultaneously, a panel of biochemical variables was monitored to evaluate liver and kidney function and possible hemodilution effects. Pharmacokinetic parameters were calculated once at baseline and once in gestational month 8. Results: Initially, LTG and LTG-GLUC serum concentrations fell simultaneously by 27% and 38%, respectively (gestational month 2). Subsequently, the ratio of the LTG-GLUC/LTG serum concentrations increased... (More)
Purpose: To investigate the physiological mechanisms behind the pronounced decline of lamotrigine (LTG) serum concentrations during pregnancy. Methods: Serum and urine concentrations of LTG and its main metabolite, LTG-N2-glucuronide (LTG-GLUC), were measured monthly in 21 pregnancies of 19 women using LTG. Simultaneously, a panel of biochemical variables was monitored to evaluate liver and kidney function and possible hemodilution effects. Pharmacokinetic parameters were calculated once at baseline and once in gestational month 8. Results: Initially, LTG and LTG-GLUC serum concentrations fell simultaneously by 27% and 38%, respectively (gestational month 2). Subsequently, the ratio of the LTG-GLUC/LTG serum concentrations increased gradually, correlating strongly with rising serum estradiol concentrations. In gestational month 8, the ratio was 164% higher than at baseline. At that time, LTG total clearance had increased by 118%, and the amount of unchanged LTG in urine had dropped by 40% while the amount of LTG-GLUC had increased by a corresponding 37%. Conclusions: The simultaneous decline of LTG and LTG-GLUC serum concentrations in early pregnancy suggests that in this phase, increased renal blood flow is the major cause. After gestational month 2, estradiol-induced glucuronidation of LTG becomes more important, leading to a further fall of LTG serum concentrations and a gradual rise of the LTG-GLUC/LTG-ratio through the remaining pregnancy. An expanded volume of distribution may also contribute to reduced LTG serum concentrations in pregnancy.
(Less)
- author
- Reimers, Arne LU ; Helde, Grethe ; Bråthen, Geir and Brodtkorb, Eylert
- publishing date
- 2011-05
- type
- Contribution to journal
- publication status
- published
- keywords
- Estradiol, Glucuronide, Lamotrigine, Pregnancy, Renal clearance, UGT1A4
- in
- Epilepsy Research
- volume
- 94
- issue
- 3
- pages
- 198 - 205
- publisher
- Elsevier
- external identifiers
-
- pmid:21356585
- scopus:79955524916
- ISSN
- 0920-1211
- DOI
- 10.1016/j.eplepsyres.2011.02.002
- language
- English
- LU publication?
- no
- id
- 8387161b-7486-498e-ba99-1c0a6872e51f
- date added to LUP
- 2024-08-31 14:51:08
- date last changed
- 2024-09-02 13:02:08
@article{8387161b-7486-498e-ba99-1c0a6872e51f,
abstract = {{<p>Purpose: To investigate the physiological mechanisms behind the pronounced decline of lamotrigine (LTG) serum concentrations during pregnancy. Methods: Serum and urine concentrations of LTG and its main metabolite, LTG-N2-glucuronide (LTG-GLUC), were measured monthly in 21 pregnancies of 19 women using LTG. Simultaneously, a panel of biochemical variables was monitored to evaluate liver and kidney function and possible hemodilution effects. Pharmacokinetic parameters were calculated once at baseline and once in gestational month 8. Results: Initially, LTG and LTG-GLUC serum concentrations fell simultaneously by 27% and 38%, respectively (gestational month 2). Subsequently, the ratio of the LTG-GLUC/LTG serum concentrations increased gradually, correlating strongly with rising serum estradiol concentrations. In gestational month 8, the ratio was 164% higher than at baseline. At that time, LTG total clearance had increased by 118%, and the amount of unchanged LTG in urine had dropped by 40% while the amount of LTG-GLUC had increased by a corresponding 37%. Conclusions: The simultaneous decline of LTG and LTG-GLUC serum concentrations in early pregnancy suggests that in this phase, increased renal blood flow is the major cause. After gestational month 2, estradiol-induced glucuronidation of LTG becomes more important, leading to a further fall of LTG serum concentrations and a gradual rise of the LTG-GLUC/LTG-ratio through the remaining pregnancy. An expanded volume of distribution may also contribute to reduced LTG serum concentrations in pregnancy.</p>}},
author = {{Reimers, Arne and Helde, Grethe and Bråthen, Geir and Brodtkorb, Eylert}},
issn = {{0920-1211}},
keywords = {{Estradiol; Glucuronide; Lamotrigine; Pregnancy; Renal clearance; UGT1A4}},
language = {{eng}},
number = {{3}},
pages = {{198--205}},
publisher = {{Elsevier}},
series = {{Epilepsy Research}},
title = {{Lamotrigine and its N2-glucuronide during pregnancy : The significance of renal clearance and estradiol}},
url = {{http://dx.doi.org/10.1016/j.eplepsyres.2011.02.002}},
doi = {{10.1016/j.eplepsyres.2011.02.002}},
volume = {{94}},
year = {{2011}},
}