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Erythromycin Effects on Multiple‐Dose Carbamazepine Kinetics

 

作者: Michael,   Miles Michael,  

 

期刊: Therapeutic Drug Monitoring  (OVID Available online 1989)
卷期: Volume 11, issue 1  

页码: 47-52

 

ISSN:0163-4356

 

年代: 1989

 

出版商: OVID

 

关键词: Carbamazepine;Erythromycin;Pharmacokinetics;Metabolism;Drug interaction.

 

数据来源: OVID

 

摘要:

To determine the effects of erythromycin on multiple-dose carbamazepine pharmacokinetics, seven healthy male volunteers were given 300–400 mg of carbamazepine each morning for 17 consecutive days. All subjects were given a placebo erythromycin form every 6 h on days 12, 13, and 14, then changed to erythromycin base 250 mg every 6 h for the final 3 days. Serial blood samples were drawn after the morning doses on days 14 and 17. Analysis of carbamazepine and carbamazepine-10,11-epoxide concentrations were made by high-performance liquid chromatography. Pharmacokinetic analysis showed carbamazepine half-life and 24-h postdose concentration to increase significantly (p < 0.05) and oral clearance to decrease (p < 0.05) during erythromycin administration. Decreases in carbamazepine-10,11-epoxideCmax(p< 0.001), area under the concentration-time curveo-24(p < 0.001), and carbamazepine-10,11-epoxide to carbamazepine ratio (p < 0.01) also occurred during carbamazepine dosing. Erythromycin significantly inhibits the epoxide-diol metabolic pathway by which carbamazepine is transformed to carbamazepine-10,11-epoxide. Wide individual variability in this interaction should serve to warn practitioners of the unpredictability of this interaction.

 

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