The effect of tenidap sodium on the disposition and plasma protein binding of phenytoin in healthy male volunteers.

Blum, R. A.; Schentag, J J; Gardner, M. J.; Wilner, K.

doi:10.1111/j.1365-2125.1995.tb04500.x

Cited by 12 publications

(2 citation statements)

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“…This indicates that tenidap does not inhibit or induce the P450IIC9 isozyme. This finding is consistent with that of a similar study which found that tenidap did not affect the clearance of phenytoin which is also metabolised by the P450IIC9 isozyme [14].…”

Section: Discussionsupporting

confidence: 93%

Tenidap sodium does not alter the clearance or plasma protein binding of tolbutamide in healthy male volunteers.

Wilner

Gardner

1995

Brit J Clinical Pharma

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Section: Discussionsupporting

confidence: 93%

Tenidap sodium does not alter the clearance or plasma protein binding of tolbutamide in healthy male volunteers.

Wilner

Gardner

1995

Brit J Clinical Pharma

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“…Blum et al reported that tenidap sodium 120 mg/day at steady state increased the percentage of free phenytoin in plasma by 25%. The authors concluded that since tenidap increases the percentage of unbound phenytoin in plasma, monitoring free phenytoin concentration should be considered (59). Reduced interaction between phenytoin and valproic acid with nonsteroidal anti-inflammatory drugs in uremia have been described.…”

Section: Drug-drug Interactions and Elevated Free Drug Concentrationsmentioning

confidence: 99%

Clinical Utility of Free Drug Monitoring

Dasgupta

2002

Clinical Chemistry and Laboratory Medicine

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Most drugs are bound to serum proteins to a various degree. Only unbound or free drug is pharmacologically active. Usually total drug is measured for therapeutic monitoring because there is equilibrium between bound and free drugs, and concentration of free drug can be predicted from total drug concentration. However, under certain conditions this equilibrium is disturbed and the measured free drug concentration can be significantly higher than expected from total drug concentrations, especially for strongly protein-bound drugs. In such case a patient may experience drug toxicity even if the total drug concentration is within the therapeutic range. Conditions like uremia, liver disease and hypoalbuminemia can lead to significant increases in free drug concentration. Therefore, monitoring free phenytoin and free valproic acid is recommended in these patients. Drug-drug interactions can also lead to a disproportionate increase in free drug concentration. One strongly protein-bound drug can significantly displace another strongly protein-bound drug if both drugs share the same binding site. Several over-the-counter pain medications such as salicylate, naproxen, and ibuprofen can cause significant displacement of both phenytoin and valproic acid from albumin binding site. Interestingly, such interactions are absent in uremic patients. Elderly patients may have increased free phenytoin or valproic acid due to hypoalbuminemia. Elevated free phenytoin concentrations have also been reported in patients with AIDS. Although digoxin is 25% bound to protein, monitoring free digoxin is useful in patients with elevated endogenous digoxin-like immunoreactive substances or in patients overdosed with digoxin and being treated with digibind. Monitoring free digoxin can also eliminate interference of Chinese medicines Chan Su and Danshen in serum digoxin measurement by certain immunoassays. However, free drug monitoring is not a routine procedure in clinical laboratories due to technical difficulties and lack of established reference ranges for free drugs.

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Free Drug Monitoring

Dasgupta

2011

Encyclopedia of Life Sciences

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Drugs are bound to various serum proteins in different degrees varying from 0% protein binding to 99% protein binding, but only unbound or free drug is pharmacologically active. Although free drug concentration can be estimated from total concentration knowing the extent of protein binding of a particular drug, for strongly bound drugs (more than 80% bound to serum protein), prediction of free level is not always possible. Conditions such as uremia, liver disease and hypoalbuminemia can lead to significant increases in free drug resulting in drug toxicity although the total drug concentration may be within the established therapeutic range. Drug–drug interactions are another major cause for disproportionate increases in free drug concentrations. Currently, free drug concentrations of anticonvulsants such as phenytoin, carbamazepine and valproic acid are widely measured in clinical laboratories. Newer drugs such as mycophenolic acid mofetil and certain protease inhibitors are also considered as good candidates for monitoring free drug concentration. Key Concepts: There are rationales for monitoring free drug concentration only for drugs that are strongly bound to serum proteins (80% or more). Why free concentrations of phenytoin, valproic acid and carbamazepine are frequently monitored in certain patient population? There is a need for monitoring free drug levels in uremia due to impaired protein binding of drugs as well as displacement of certain drugs from protein binding by ceratin uremic toxins. There is a need for monitoring free drug concentrations in hepatic diseases due to impaired protein binding of certain drugs. There is a need for monitoring free drug concentration in patients with hypoalbuminemia and critically ill patients due to elevated concentrations of free levels of drugs secondary to impaired protein binding. There is a need for monitoring free drug concentrations in pregnancy due to change in protein binding and various other factors that affect clearance of certain drugs. There is a need for monitoring free drug concentrations in AIDS patients due to impaired protein binding and probable drug–drug interactions. Future candidates for monitoring free drugs include mycophenolic acid and protease inhibitors because these drugs are strongly bound to albumin and also have narrow therapeutic index. Special case of monitoring free drug concentrations is digoxin, which is only 25% bound to serum proteins, but monitoring free digoxin in patients being treated with Digibind or taking certain herbal supplements is helpful to get clinically meaningful results.

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The effect of tenidap sodium on the disposition and plasma protein binding of phenytoin in healthy male volunteers.

Cited by 12 publications

References 11 publications

Tenidap sodium does not alter the clearance or plasma protein binding of tolbutamide in healthy male volunteers.

Tenidap sodium does not alter the clearance or plasma protein binding of tolbutamide in healthy male volunteers.

Clinical Utility of Free Drug Monitoring

Free Drug Monitoring

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