Correlating blood and urinary concentrations of clobazam doses in Japanese children and adolescents with intractable epilepsy.
Clobazam (CLB) is an antiepileptic drug that is metabolized to the major metabolite N-desmethylclobazam (N-CLB). Our aim was to evaluate the utility of corrected urinary concentrations of CLB and N-CLB in Japanese children and adolescents with epilepsy. Blood and urinary concentrations of CLB and N-CLB were evaluated in 42 patients. The urinary and peak blood concentrations were measured 2-3 h after the last dose. The ratio of the blood and urinary creatinine concentrations was used to calculate the corrected urinary concentrations. A moderate correlation was found between the CLB dose and the CLB serum concentration, but this correlation was not found for N-CLB. Patients were dichotomized based on two regression lines, which were detected by statistical analyses with a cumulative distribution function: the lower ratio group (CLB/N-CLB < 0.275) and the higher ratio group (≥0.275). Moderate correlations were observed between the CLB dose and the serum concentration or the corrected value of CLB for the lower ratio group, and moderate to strong correlations were observed for the higher ratio group. The corrected urinary concentration of CLB correlates to the CLB dose when stratified by the CLB/N-CLB ratio and may prove practical for clinical estimation of the CLB serum concentration.
Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Toshiyuki
T
Iwasaki
Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Yutaka
Y
Nonoda
Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Tomoya
T
Ishida
Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Taira
T
Toki
Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Masahiro
M
Ishii
D000284:Administration, Oral; D000293:Adolescent; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood / Q000652:urine; D044466:Asian People; D001569:Benzodiazepines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*; D002648:Child; D002675:Child, Preschool; D000078306:Clobazam; D000069279:Drug Resistant Epilepsy / Q000097:blood* / Q000188:drug therapy / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D055815:Young Adult
D000927:Anticonvulsants; D001569:Benzodiazepines; D000078306:Clobazam; C024581:N-desmethylclobazam
N-desmethylclobazam; clobazam; clobazam/N-desmethylclobazam ratio; creatinine coefficient; urinary concentration