SIGNIFICANT WEIGHT-REDUCTION IN OBESE SUBJECTS ENHANCES CARBAMAZEPINE ELIMINATION

被引:37
作者
CARACO, Y
ZYLBERKATZ, E
BERRY, EM
LEVY, M
机构
[1] Division of Medicine, Clinical Pharmacology and Metabolic Unit, Hadassah University Hospital
关键词
D O I
10.1038/clpt.1992.54
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Single-dose (200 mg) carbamazepine pharmacokinetics was evaluated in six obese, otherwise healthy subjects, before and after a mean +/- SEM weight reduction of 30.0 +/- 5.0 kg over 11.3 +/- 1.2 months. After weight loss the mean +/- SEM plasma elimination half-life (t1/2) or carbamazepine was significantly shortened (60.3 +/- 3.1 versus 30.8 +/- 3.3 hours, p < 0.01) and the total plasma clearance (CL) increased (20.4 +/- 1.8 versus 31.6 +/- 5.0 ml/min, p < 0.05). The apparent volume of distribution (V(area)) decreased (106.2 +/- 9.9 versus 77.7 +/- 4.5 L, p < 0.01); however, no difference was evident when carbamazepine V(area) was corrected for body weight. In addition, weight loss coincided in all participants with a complete sonographic disappearance of the inital fatty liver infiltration noted on enrollment. In conclusion, obesity associated with fatty liver presents an enlarged carbamazepine V(area), prolonged carbamazepine t1/2, and reduced carbamazepine CL. Whenever carbamazepine is initiated in obese subjects, steady-state concentrations should be expected only after twice the time required to achieve steady state in lean subjects. Thus carbamazepine maintenance dose should be reduced, dose interval prolonged, and monitoring of carbamazepine plasma levels provided.
引用
收藏
页码:501 / 506
页数:6
相关论文
共 24 条
  • [1] DRUG DISPOSITION IN OBESE HUMANS - AN UPDATE
    ABERNETHY, DR
    GREENBLATT, DJ
    [J]. CLINICAL PHARMACOKINETICS, 1986, 11 (03) : 199 - 213
  • [2] ABERNETHY DR, 1981, J PHARMACOL EXP THER, V217, P681
  • [3] LIDOCAINE DISPOSITION IN OBESITY
    ABERNETHY, DR
    GREENBLATT, DJ
    [J]. AMERICAN JOURNAL OF CARDIOLOGY, 1984, 53 (08) : 1183 - 1186
  • [4] ALEXANDER J K, 1962, Cardiovasc Res Cent Bull, V1, P39
  • [5] Alexander J K, 1980, Curr Probl Cardiol, V5, P1, DOI 10.1016/0146-2806(80)90013-4
  • [6] EFFECT OF WEIGHT-LOSS ON CARDIAC CHAMBER SIZE, WALL THICKNESS AND LEFT-VENTRICULAR FUNCTION IN MORBID-OBESITY
    ALPERT, MA
    TERRY, BE
    KELLY, DL
    [J]. AMERICAN JOURNAL OF CARDIOLOGY, 1985, 55 (06) : 783 - 786
  • [7] BLOUIN RA, 1987, CLIN PHARMACY, V6, P706
  • [8] BROUWER KLR, 1984, J PHARMACOL EXP THER, V231, P654
  • [9] CLAIN DJ, 1987, GASTROENTEROL CLIN N, V16, P239
  • [10] OBESITY AND CARDIAC-FUNCTION
    DEDIVITIIS, O
    FAZIO, S
    PETITTO, M
    MADDALENA, G
    CONTALDO, F
    MANCINI, M
    [J]. CIRCULATION, 1981, 64 (03) : 477 - 482