Influence of gestational age and body weight on the pharmacokinetics of labetalol in pregnancy.
Influence of gestational age and body weight on the pharmacokinetics of labetalol in pregnancy.
复制标题
妊娠年龄和体重对妊娠Labetalol药代动力学的影响。
DOI：
10.1007/s40262-013-0123-0
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发表时间：
2014-04
影响因子：
4.5
通讯作者：
Rodvold, Keith A.
中科院分区：
文献类型：
--
作者：
Fischer, James H.;Sarto, Gloria E.;Hardman, Jennifer;Endres, Loraine;Jenkins, Thomas M.;Kilpatrick, Sarah J.;Jeong, Hyunyoung;Geller, Stacie;Deyo, Kelly;Fischer, Patricia A.;Rodvold, Keith A.
Labetalol is frequently prescribed for treatment of hypertension during pregnancy. However, the influence of pregnancy on labetalol pharmacokinetics is uncertain, with inconsistent findings reported by previous studies. This study examined the population pharmacokinetics of oral labetalol during and after pregnancy in women receiving labetalol for hypertension. Data were collected from 57 women receiving the drug for hypertension from the 12th week of pregnancy through 12 weeks postpartum using a prospective, longitudinal design. A sparse sampling strategy guided collection of plasma samples. Samples were assayed for labetalol by high performance liquid chromatography. Estimation of population pharmacokinetic parameters and covariate effects was performed by nonlinear mixed effects modeling using NONMEM. Final population model was validated by bootstrap analysis and visual predictive check. Simulations were performed with the final model to evaluate the appropriate body weight to guide labetalol dosing. Lean body weight (LBW) and gestational age, i.e., weeks of pregnancy, were identified as significantly influencing oral clearance (CL/F) of labetalol, with CL/F ranging from 1.4-fold greater than postpartum values at 12 weeks gestational age to 1.6-fold greater at 40 weeks. Doses adjusted for LBW provide more consistent drug exposure than doses adjusted for total body weight. The apparent volumes of distribution for the central compartment and at steady-state were 1.9-fold higher during pregnancy. Gestational age and LBW impact the pharmacokinetics of labetalol during pregnancy and have clinical implications for adjusting labetalol doses in these women.
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影响因子：
--
作者：
Du Bois, D;Du Bois, EF
通讯作者：
Du Bois, EF
影响因子：
6.7
作者：
LALONDE, RL;OREAR, TL;BOTTORFF, MB
通讯作者：
BOTTORFF, MB
DOI：
10.1016/s0378-4347(00)84725-8
发表时间：
1984-01-01
期刊：
JOURNAL OF CHROMATOGRAPHY
影响因子：
--
作者：
ALTON, KB;LEITZ, F;PATRICK, J
通讯作者：
PATRICK, J
影响因子：
2.6
作者：
Andrade, Susan E.;Raebel, Marsha A.;Platt, Richard
通讯作者：
Platt, Richard
影响因子：
2.9
作者：
Carvalho, Teresa Maria J. P.;Cavalli, Ricardo de Carvalho;Lanchote, Vera Lucia
通讯作者：
Lanchote, Vera Lucia