How do you calculate valproic acid levels?
In 121 adult patients, with albumin levels of 18 – 41 g/L, the total concentration of valproic acid was normalized using the derived equation: C(N) = alpha(H)C(H)/6.5, where alpha(H) is the free fraction of the drug corresponding to the patient’s particular albuminemia and C(H) is the total concentration of valproic …
What is pharmacokinetics of sodium valproate?
Pharmacokinetics. Plasma protein binding was measured at the therapeutic concentration of 80 JLg/ml. The binding varied between 80% to 94% in the healthy subjects. Increasing VPA above the therapeutic range to concentrations of 150 and 300 /Lg/ml resulted in lower binding, about 70% and 35%, respectively.
What is the mechanism of action for valproic acid?
Mechanism of Action
Valproic acid exhibits its pharmacologic effects in a couple of ways, such as by acting on GABA (γ aminobutyric acid) levels in the CNS, blocking voltage-gated ion channels, and inhibiting histone deacetylase.
What labs should be monitored when taking valproic acid?
Obtain baseline complete blood cell counts with differential (CBC with diff); liver function tests, and pregnancy test for females. Monitor Depakote levels, liver function tests, and CBC with diff every 3-6 months.
How do you calculate free valproate?
For measurements with serum albumin levels below 18 g/L or above 42 g/L, the free VPA fraction was calculated using the original equation y = A・e −BX (y = free VPA fraction; A = 130.69; B = 4.96・10−3; r = −0.82; X = serum albumin [μmol/L]) by Parent et al.
When do you draw valproic levels?
It is recommended that trough levels for the DR version be drawn immediately prior to the morning dose, assuming a twice-daily dosing strategy. For once-daily divalproex ER regimens, the ideal time to draw serum levels is immediately prior to the next scheduled dose.
Does valproate have linear pharmacokinetics?
Valproic acid follows nonlinear pharmacokinetics owing to saturable, or concentration-dependent, plasma protein binding. This is the type of nonlinear pharmacokinetics that occurs when the number of drug molecules overwhelms or saturates albumin’s ability to bind the drug in the plasma.
How is valproic acid metabolized?
Valproic acid is eliminated via extensive hepatic metabolism to several metabolites [14]. Its major metabolic pathways are glucuronidation and mitochondrial β-oxidation, while CYP-dependent oxidation is only a minor pathway [15].
What are the effects of valproic acid?
Taking too much valproic acid can lead to symptoms such as: feeling or being sick (nausea or vomiting) headaches, or feeling dizzy. muscle weakness.
How does valproic acid increase GABA?
These results suggest that high doses of valproate may increase brain GABA by interfering with intermediate metabolism, possibly at the level of medium chain acyl CoA. However alterations in brain GABA did not correlate with anticonvulsant activity.
When do you monitor valproate levels?
It is observed that measuring serum VPA levels at 24 h is recommended and provides a more accurate value for patients on OD dosage. Measuring it at 12 h in case of OD dosing would give a 1.3 times higher value than the actual trough value.
What is a free valproic acid level?
The generally acceptable range for total valproic acid used as a reference to guide therapy is 50 to 125 mcg/mL. The corresponding range of free valproic acid concentration for clinical reference is 5 to 25 mcg/mL.
How does valproic acid work for bipolar?
Valproic acid is an anticonvulsant (or anti-epileptic) medicine. It’s not fully understood how this medicine works for treating bipolar disorder. However valproic acid is thought to reduce or prevent manic episodes by increasing the amount of a chemical called gamma-aminobutyric acid (GABA) in the brain.
Does it really matter when a blood sample for valproic acid concentration is taken following once-daily administration of divalproex-ER?
The greatest deviation from trough VPA concentration occurs around the peak, that is 3 to 15 hours after a once-daily divalproex-ER dose; sampling during this time period is recommended only if a clinical need exists to test for a higher VPA concentration.
What is the half life of valproic acid?
Valproic acid, commonly used in neuropsychiatry, has an elimination half-life of 4-16 hours in different populations (children vs adults, enzyme-induced vs uninduced). Divalproex-ER, a once-daily extended- release divalproex sodium formulation, is designed to release valproic acid over >18 hours.
Is valproic acid linear kinetics?
Valproic acid follows nonlinear pharmacokinetics due to saturable, or concentration-dependent, plasma protein binding. This is the type of nonlinear pharmacokinetics that occurs when the number of drug molecules overwhelms or saturates albumin’s ability to bind the drug in the plasma.
What metabolizes valproic acid?
VPA is a fatty acid and can be metabolized via endogenous pathways in the mitochondria. It has been observed that some of the mitochondrial metabolites of VPA generated by this pathway are hepatotoxic.
What is the difference between valproate and valproic acid?
Valproic acid is the protonated form — in case that term doesn’t bring back memories from biochemistry, that means that the compound is bonded to a proton (H+). Sodium valproate, on the other hand, is the sodium salt of valproic acid.
What is another name for valproic acid?
Valproic (val-PRO-ik) acid is the generic name (non-brand name) of a widely used type of seizure medicine. The brand-name form of valproic acid in the United States and Canada is Depakene.
What neurotransmitter does valproic acid affect?
GABA is a neurotransmitter, a signaling molecule in the brain, that inhibits the activity of brain cells, or neurons. Valproic acid may also block the reuptake of GABA, thereby increasing GABA levels in the brain.
Does valproic acid increase serotonin?
Valproic acid may displace protein-bound serum tryptophan thereby increasing brain tryptophan which is converted to serotonin.
What can cause valproic acid levels to drop?
Background: The plasma concentrations of valproic acid (VPA) are known to decrease during the concomitant administration of carbapenem antibiotics, such as meropenem, imipenem, and ertapenem.
Why valproic acid test is done?
A valproic acid test measures the amount of valproic acid, which is an anticonvulsant medicine, in a blood sample. Valproic acid is prescribed primarily to prevent seizures. The seizure disorder epilepsy is a nervous system condition that causes electrical signals in the brain to misfire.
What is valproic acid level total?
Valproic Acid, Total. Therapeutic Range: 50-125 µg/mL. Toxic: Greater than 150 µg/mL.