Abstract
The diurnal fluctuations in free and total plasma levels of carbamazepine (CBZ) and carbamazepine-10, ll-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.
| Original language | English |
|---|---|
| Pages (from-to) | 408-413 |
| Number of pages | 6 |
| Journal | Therapeutic Drug Monitoring |
| Volume | 6 |
| Issue number | 4 |
| Publication status | Published - 1984 |
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Keywords
- Carbamazepine
- Carbamazepine-epoxide
- Diurnal fluctuations
- Free plasma concentrations
- Side effects
ASJC Scopus subject areas
- Pharmacology (medical)
- Pharmacology
- Toxicology
- Health, Toxicology and Mutagenesis
- Biochemistry
- Biochemistry, Genetics and Molecular Biology(all)
- Public Health, Environmental and Occupational Health
Cite this
Free and total plasma concentrations of carbamazepine and carbamazepine-10,11-epoxide in epileptic patients : Diurnal fluctuations and relationship with side effects. / Riva, R.; Contin, M.; Albani, F.; Perucca, E.; Ambrosetto, G.; Gobbi, G.; Coltelli, P.; Procaccianti, G.; Baruzzi, A.
In: Therapeutic Drug Monitoring, Vol. 6, No. 4, 1984, p. 408-413.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Free and total plasma concentrations of carbamazepine and carbamazepine-10,11-epoxide in epileptic patients
T2 - Diurnal fluctuations and relationship with side effects
AU - Riva, R.
AU - Contin, M.
AU - Albani, F.
AU - Perucca, E.
AU - Ambrosetto, G.
AU - Gobbi, G.
AU - Coltelli, P.
AU - Procaccianti, G.
AU - Baruzzi, A.
PY - 1984
Y1 - 1984
N2 - The diurnal fluctuations in free and total plasma levels of carbamazepine (CBZ) and carbamazepine-10, ll-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.
AB - The diurnal fluctuations in free and total plasma levels of carbamazepine (CBZ) and carbamazepine-10, ll-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.
KW - Carbamazepine
KW - Carbamazepine-epoxide
KW - Diurnal fluctuations
KW - Free plasma concentrations
KW - Side effects
UR - http://www.scopus.com/inward/record.url?scp=0021739710&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0021739710&partnerID=8YFLogxK
M3 - Article
C2 - 6542700
AN - SCOPUS:0021739710
VL - 6
SP - 408
EP - 413
JO - Therapeutic Drug Monitoring
JF - Therapeutic Drug Monitoring
SN - 0163-4356
IS - 4
ER -