Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028738 (nystagmus)
 7,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence of lateral gaze nystagmus and its correlation with free and total plasma concentrations of carbamazepine (CBZ) and carbamazepine-10, 11-epoxide (CBZ-E) were examined in 97 epileptic patients receiving chronic treatment with CBZ alone (n = 54) or in combination with phenobarbital (PB) (n = 43). All patients had plasma CBZ concentrations within the clinically optimal range (less than 50 mumol/L). Nystagmus was seen in 26% of patients receiving monotherapy and in 33% receiving combination therapy. Within each group, however, nystagmus was much more frequent among patients with higher CBZ concentrations. For patients receiving PB in combination the CBZ levels above which nystagmus was particularly frequent appeared to be lower than in the monotherapy patients--a finding that could not be attributed to differences in plasma PB concentrations. The correlation of CBZ-E levels (or the sum of CBZ + CBZ-E) with the occurrence of nystagmus was no better than that observed with CBZ levels alone. Free drug levels did not appear to be superior to total levels in discriminating between patients with or without nystagmus. These results indicate that the occurrence of nystagmus is concentration-dependent within the therapeutic plasma CBZ concentration range and suggest that the threshold at which this neurological sign appears is reduced in the presence of PB, possibly as a result of a pharmacodynamic interaction.
Ther Drug Monit 1985
PMID:Lateral gaze nystagmus in carbamazepine-treated epileptic patients: correlation with total and free plasma concentrations of parent drug and its 10,11-epoxide metabolite. 404 64

The diurnal fluctuations in free and total plasma levels of carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZ-E) and their relationship with intermittent side effects were examined in 10 epileptic patients stabilized on chronic CBZ therapy alone or in combination with phenobarbital (PB). With a t.i.d. or q.i.d. dosing schedule, total plasma levels of CBZ and CBZ-E fluctuated to a similar extent (average 34% and 29%, respectively). The diurnal changes in free levels of both compounds mirrored closely those of the total levels. Free fraction values ranged from 13 to 26% for CBZ and from 24 to 66% for CBZ-E. Owing to the lower protein binding of the metabolite, CBZ-E/CBZ ratios were higher in plasma water (0.49) than in whole plasma (0.22). A good correlation was found between both total and free CBZ levels and dose-related side effects (diplopia, nystagmus). On the other hand, no apparent relationship was found between side effects and either total or free plasma CBZ-E. The correlation with the presence of neurological signs of toxicity for the sum of CBZ + CBZ-E levels was no better than that observed for CBZ levels alone. These data do not support the hypothesis that CBZ-E contributes significantly to the development of dose-related side effects in CBZ-treated patients.
Ther Drug Monit 1984
PMID:Free and total plasma concentrations of carbamazepine and carbamazepine-10,11-epoxide in epileptic patients: diurnal fluctuations and relationship with side effects. 654

Phenytoin is an effective anticonvulsant, but high serum phenytoin concentrations may be associated with serious toxicity. The upper limit for the therapeutic serum concentration of phenytoin is considered to be 80 micromol/L. However, in some situations higher serum concentrations are needed to control seizures. The authors describe a 9-year-old girl who needed concentrations twice the normal amount to control recurrent episodes of decreased levels of consciousness. Except for nystagmus, she had no other signs of phenytoin toxicity. This patient highlights the critical principle in therapeutic drug monitoring of individualizing drug therapy. Although some patients receiving phenytoin may achieve seizure control with "subtherapeutic" levels (i.e., <40 micromol/L), others may need supratherapeutic levels, as was the case with this patient. Clinicians should be careful not to treat "numbers" (i.e., serum concentrations), but rather the patient's clinical condition, with a careful balance between therapeutic advantage and adverse effects.
Ther Drug Monit 2002 Jun
PMID:How high can we go with phenytoin? 1202 30