A pharmacokinetic study to determine the drug interaction between valproate and propranolol.
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 VFA metabolism is not affected by coadministration of propranolol in this group of patients.
Nemire
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Department of Neurology, Texas Tech University Health Sciences Center, Lubbock 79430, USA.
Toledo
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CA
Ramsay
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D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000627:therapeutic use*; D012640:Seizures / Q000188:drug therapy; D014635:Valproic Acid / Q000097:blood / Q000493:pharmacokinetics*
D000927:Anticonvulsants; D000959:Antihypertensive Agents; D014635:Valproic Acid; D011433:Propranolol