TY - JOUR
T1 - Significant weight reduction in obese subjects enhances carbamazepine elimination
AU - Caraco, Yoseph
AU - Zylber-Katz, Ester
AU - Berry, Elliot M.
AU - Levy, Micha
PY - 1992
Y1 - 1992
N2 - 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) of 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 (Varea) decreased (106.2 ± 9.9 versus 77.7 ± 4.5 L, p < 0.01); however, no difference was evident when carbamazepine Varea 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 Varea, 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 monitor-ing of carbamazepine plasma levels provided.
AB - 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) of 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 (Varea) decreased (106.2 ± 9.9 versus 77.7 ± 4.5 L, p < 0.01); however, no difference was evident when carbamazepine Varea 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 Varea, 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 monitor-ing of carbamazepine plasma levels provided.
UR - http://www.scopus.com/inward/record.url?scp=0026537888&partnerID=8YFLogxK
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C2 - 1587063
AN - SCOPUS:0026537888
SN - 0009-9236
VL - 51
SP - 501
EP - 506
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
IS - 5
ER -