Association between patient age and gabapentin serum concentration-to-dose ratio: a preliminary multivariate analysis.
OBJECTIVE
To evaluate the association between patient age and gabapentin (GBP) concentration-to-dose ratio by a multivariate analysis.


METHODS
The association between patient age and the trough steady-state serum concentration of gabapentin (GBP) normalized to 1 mg/kg body weight or concentration-to-dose ratio (CDR) was retrospectively assessed by analysis of covariance. Potential confounding factors considered were GBP dosage, the number of GBP doses per day, and the presence of concomitant antiepileptic drugs (AEDs). Concentrations that had been measured in predose "trough" samples collected from 66 patients, aged 5-84 years, with partial seizures or neuropathic pain chronically receiving GBP BID (n = 21) or TID (n = 45), alone (n = 15) or in combination with other AEDs (n = 51) were used in this retrospective analysis.


RESULTS
Average GBP CDR was 0.23 +/- 0.18 (mean +/- SD). The GBP CDR increased with age (r2 = 0.46, P < 0.001), and the correlation was improved when only samples from patients taking GBP BID were separately considered (r2 = 0.68, P < 0.001). The ratio was lower in the 10 children younger than 11 years of age (0.07 +/- 0.05) than in 8 adolescents aged 12 to 18 years (0.14 +/- 0.04), lower than in 35 adults aged 19 to 65 years (0.22 +/- 0.13), and lower than in 13 patients older than 65 years of age (0.45 +/- 0.20) by 1-way analysis of variance (F = 19.4, P < 0.001). Analysis of covariance showed a significant influence on GBP CDR of patient age (P < 0.001) and the number of GBP daily doses (P < 0.01), but GBP daily dosage or concomitant AEDs had no significant influence on the ratio.


CONCLUSIONS
In this retrospective study of a small, select group of patients, (1) the GBP CDR increased significantly with age when potential confounding factors such as GBP dosage, number of GBP doses per day, and concomitant AEDs were considered by analysis of covariance, and (2) patients older than 65 years, even without any known renal disease, may have double GBP CDR than younger adults and, therefore, may need half of the GBP dose per body weight to achieve a similar concentration.
Armijo
Juan A
JA
Service of Clinical Pharmacology, Marqués de Valdecilla University Hospital, University of Cantabria School of Medicine, Santander, Spain. facasj@humv.es
Pena
María A
MA
Adín
Javier
J
Vega-Gil
Noelia
N
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood* / Q000187:drug effects; D000588:Amines / Q000008:administration & dosage* / Q000097:blood*; D000704:Analysis of Variance; D002648:Child; D002675:Child, Preschool; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage* / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D005260:Female; D000077206:Gabapentin; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012189:Retrospective Studies; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage* / Q000097:blood*
D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin