TY - JOUR
T1 - Valproic acid plasma concentration decreases in a dose-independent manner following administration of meropenem
T2 - A retrospective study
AU - Haroutiunian, Simon
AU - Rabinovich, Bella
AU - Adam, Miriam
AU - Hoffman, Amnon
AU - Ratz, Yael
PY - 2009/11
Y1 - 2009/11
N2 - Several case reports indicate that carbapenem antibiotics, especially meropenem, may decrease the plasma concentrations of valproic acid (VPA), thus decreasing its therapeutic activity. To investigate the onset, severity, and dose dependency of the interaction between meropenem and VPA, the authors carried out a retrospective evaluation of data collected during 24 months from patients hospitalized in a tertiary medical center. The analysis included 36 patients. VPA mean ± SEM plasma concentration decreased from of 50.8 ± 4.5 ?μ g/mL to 9.9 ± 2.1 μg/mL (P <.001) following meropenem administration. After discontinuation of meropenem, VPA plasma concentrations remained low for 7 days and then gradually increased after 8 to 14 days, reaching values comparable to those before meropenem initiation. Different daily VPA doses showed a similar pattern of decreased VPA concentrations. The mean decrease in individual plasma VPA concentration was 82.1% ± 2.7%. The mean VPA plasma concentration of patients in whom samples were drawn within 24 hours of meropenem initiation was 9.9 ± 3.2 μ g/mL. In conclusion, the interaction between meropenem and VPA causes a significant decrease in VPA plasma concentration, apparently within 24 hours. As the therapeutic effects of VPA are plasma concentration dependent, the data suggest that these drugs should not be administered concomitantly.
AB - Several case reports indicate that carbapenem antibiotics, especially meropenem, may decrease the plasma concentrations of valproic acid (VPA), thus decreasing its therapeutic activity. To investigate the onset, severity, and dose dependency of the interaction between meropenem and VPA, the authors carried out a retrospective evaluation of data collected during 24 months from patients hospitalized in a tertiary medical center. The analysis included 36 patients. VPA mean ± SEM plasma concentration decreased from of 50.8 ± 4.5 ?μ g/mL to 9.9 ± 2.1 μg/mL (P <.001) following meropenem administration. After discontinuation of meropenem, VPA plasma concentrations remained low for 7 days and then gradually increased after 8 to 14 days, reaching values comparable to those before meropenem initiation. Different daily VPA doses showed a similar pattern of decreased VPA concentrations. The mean decrease in individual plasma VPA concentration was 82.1% ± 2.7%. The mean VPA plasma concentration of patients in whom samples were drawn within 24 hours of meropenem initiation was 9.9 ± 3.2 μ g/mL. In conclusion, the interaction between meropenem and VPA causes a significant decrease in VPA plasma concentration, apparently within 24 hours. As the therapeutic effects of VPA are plasma concentration dependent, the data suggest that these drugs should not be administered concomitantly.
KW - Drug-drug interaction
KW - Epilepsy
KW - Meropenem
KW - Pharmacokinetics
KW - Valproic acid
UR - http://www.scopus.com/inward/record.url?scp=70350407479&partnerID=8YFLogxK
U2 - 10.1177/0091270009334377
DO - 10.1177/0091270009334377
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C2 - 19773524
AN - SCOPUS:70350407479
SN - 0091-2700
VL - 49
SP - 1363
EP - 1369
JO - Journal of Clinical Pharmacology
JF - Journal of Clinical Pharmacology
IS - 11
ER -