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A Pharmacokinetic Study to Determine the Drug Interaction between Valproate and Propranolol
Author(s) -
Nemire Ruth E.,
Toledo Cynthia A.,
Ramsay R. Eugene
Publication year - 1996
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1996.tb03033.x
Subject(s) - propranolol , drug interaction , pharmacokinetics , drug , placebo , pharmacology , valproic acid , medicine , anticonvulsant , epilepsy , anesthesia , alternative medicine , pathology , psychiatry
A 40‐year‐old female receiving divalproex sodium (VPA) monotherapy for epilepsy developed a tremor secondary to the drug. Propranolol treatment was initiated. While receiving propranolol 40 mg, VPA clearance was reduced from 1.66 L/hr to 1.19 L/hr and dropped to 1.08 L/hr on propranolol 80 mg. The mechanism of this interaction is unknown. To evaluate the potential for a drug interaction between these two agents, 12 patients on VPA monotherapy, ages 19–55, were studied. The subjects were maintained on a constant dose of VPA. Each was then randomly assigned to receive placebo, or long‐acting propranolol 60 mg/day or 120 mg/day. Mean VPA serum concentrations did not change among the three groups. Plasma half‐life of VPA ranged from 7.3–18 hours and did not change with coadministration of propranolol. We concluded that VPA metabolism is not affected by coadministration of propranolol in this group of patients.