Juan A Armijo1, María A Pena, Javier Adín, Noelia Vega-Gil. 1. Service of Clinical Pharmacology, Marqués de Valdecilla University Hospital, University of Cantabria School of Medicine, Santander, Spain. facasj@humv.es
Abstract
OBJECTIVES: 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.
OBJECTIVES: 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 GBPCDR was 0.23 +/- 0.18 (mean +/- SD). The GBPCDR 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 GBPCDR 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 GBPCDR 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 GBPCDR than younger adults and, therefore, may need half of the GBP dose per body weight to achieve a similar concentration.
Authors: Ghada F Ahmed; Sai Praneeth R Bathena; Richard C Brundage; Ilo E Leppik; Jeannine M Conway; Janice B Schwartz; Angela K Birnbaum Journal: AAPS J Date: 2017-01-09 Impact factor: 4.009