Influence of age and comedication on steady-state clonazepam serum level-dose ratios in Japanese epileptic patients.
BACKGROUND
In antiepileptic drugs, the marked inter- and intrapatient variability of the level-dose ratio makes it difficult to predict serum concentrations from the administered per kg dose. It is therefore important to identify factors, such as age and comedication, that could contribute to this observed variability.


OBJECTIVE
To investigate the effect of age and comedication on clonazepam (CZP) level-dose (L/D) ratios.


METHODS
A retrospective evaluation of data from 137 epileptic patients who had received clonazepam.


RESULTS
The CZP L/D ratio increased slowly with age up to 15 years in patients on monotherapy. Associated antiepileptic therapy affected the CZP L/D ratio, which was significantly reduced in patients on polytherapy as compared to patients on monotherapy.


CONCLUSIONS
The study therefore suggests that routine monitoring of CZP serum levels is extremely useful, especially in the paediatric age group, and in patients who require associated antiepileptic medication.
Yukawa
E
E
Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. yukawa@shunsan.phar.kyushu-u.ac.jp
Satou
M
M
Nonaka
T
T
Yukawa
M
M
Ohdo
S
S
Higuchi
S
S
Kuroda
T
T
Goto
Y
Y
D000293:Adolescent; D000367:Age Factors; D000927:Anticonvulsants / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D002998:Clonazepam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy* / Q000208:ethnology; D005260:Female; D006801:Humans; D007223:Infant; D007564:Japan; D008297:Male; D012044:Regression Analysis; D012189:Retrospective Studies
D000927:Anticonvulsants; D002998:Clonazepam