Pharmacokinetics of Felbamate in Pediatric and Adult Beagle Dogs

Abstract

The relative bioavailability and pharmacokinetics of felbamate (FBM) after a single oral dose and after 10 once-daily oral doses of 60 mg/kg were investigated in adult and pediatric dogs of both sexes. The pediatric and adult dogs were aged 4-6 weeks and 1-2 years, respectively. Analysis of variance (ANOVA) was performed on the bioavailability parameters among all groups and between the first and last doses. No sex-related differences in bioavailability and pharmacokinetic parameters were observed. The bioavailability of FBM in pediatric dogs was significantly less as compared with that in adult dogs. Rapid overall elimination of the drug in pediatric dogs appears to be responsible for the lower bioavailability. The bioavailability of FBM after the last dose was also significantly lower than after the first dose for both age groups. No major differences in the rate constant of FBM absorption (ka) and volume of distribution at steady state (VSS) were observed between the two age groups. As with other clinically useful antiepileptic drugs (AEDs), higher doses of FBM may be required in pediatric populations to achieve optimum drug levels, assuming that age-related changes in FBM disposition will also be confirmed in humans.

Pharmacokinetics and dynamics of mycophenolate mofetil after single‐dose oral administration in juvenile dachshunds

“…However, these drugs are not without risks including myelosuppression, hepatotoxicity, gastrointestinal disturbances, and other drug‐specific systemic effects; therefore, regular monitoring of complete blood counts (CBC), serum biochemistry, and where possible, effective concentrations are recommended (Viviano, ). In pediatric animals, immunosuppression poses additional challenges in part due to age‐related differences in drug metabolism, where existing safety, efficacy and toxicity data may lack accuracy when doses are extrapolated from studies in adult animals to younger immature dogs (Adusumalli, Gilchrist, Wichmann, Kucharczyk, & Sofia, ; Tassinari, Benson, Elayan, Espandiari, & Davis‐Bruno, ).…”

Characteristics of selected second-generation antiepileptic drugs used in dogs

“…It also easily crossed the blood-brain barier (BBB), as was demonstrated by the above mentioned authors. The volume of distribution (Vd) of this agent was 0.9 to 1.1 L/kg (Table 2), however, in pediatric dogs the value reached 1.2-1.9 L/kg (Adusumalli et al 1992). FBM bound with plasma proteins from 22 to 25% (Table 2) and the albumin was responsible for most of the binding.…”

“…The time of maximum concentration (t max ) of FBM was reached in 4.0 to 5.5 h after the single and multiple oral dose, respectively and was not dependent on dose value. However, in pediatric dogs t max was about 3.0 h (Adusumalli et al 1992). Adusumalli et al (1991) proved that FBM is distributed readily into tissues and did not appear to accumulate in any particular tissue.…”

“…This agent also has an effect on ion channels such as the α-subunit of Na + currents and high-voltage-activated Ca 2+ channels (L-type) (Stefani et al 1996, Taglialatela et al 1996. Adusumalli et al 1991Adusumalli et al , 1992Young et al 1991Young et al , 1992 GBP 50 80 1.0 2.2-4.0 3.5-4.0 3 99 0.3-1.0 Vollmer et al 1986;Radulovic et al 1995 Matsumoto et al 1983;Boothe and Perkins 2008;Orito et al 2008 FBM -felbamate, GBP -gabapentin, LEV -levitiracetam, OXC -oxcarbazepine, TPM -topiramate, ZNS -zonisamide, F -absolute bioavailability, Vd -volume of distribution, t 1/2kel -half-life in elimination phase, CL -total body clearance, Nd -no data Following single oral administration of FBM at a dose of 11 mg/kg, approximately 100% (Table 2) was absorbed and absolute bioavailability (F) was unaffected by food (Adusumalli et al 1991). Adusumalli et al (1991Adusumalli et al ( , 1992 demonstrated that after multiple oral administration the maximal concentration (C max ) and area under the curve (AUC) were significantly smaller than in the single oral dose.…”

Percutaneous Absorption and Disposition of [14C]Chlordecone in Young and Adult Female Rats

“…Boudinot et al (1993) reported age differences in the kinetics of piroxicam in rats. Adusumalli et al (1992), Yang et al (1992), Vermeulen et al (1992), and Rumore and Blaiklock (1992) have also reported age dependence in kinetics of drugs in humans, dogs, and rats. However, a paucity of information exists for age-dependent pharmacokinetics of pesticides.…”