Circadian effect on carbamazepine kinetics in rat

Abstract

The purpose of the present study was to investigate whether the time of day (24 h) at which carbamazepine is administered influences its pharmacokinetics in the rat. The pharmacokinetics of a single, 100 mg . kg-1 bodyweight per os, dose of carbamazepine were studied at four different fixed time points of a 24-hour period (i.e. 10.00, 16.00, 22.00 or 04.00 h) in Wistar AF-SPF adult male rats maintained under controlled environmental conditions (LD: 18.00 - 06.00h) during October 1978. The total plasma levels and the unbound fraction were measured according to an immunoenzymatic method (EMIT). The effects of fasting were also investigated. The data shows circadian variations of pharmacokinetic parameters: the maximum peak concentration and the maximum time to reach this peak was observed when the drug was given respectively at 16.00h and at 10.00h. The elimination half-life varied from 15.15 hours at 16.00h to 10.48 hours at 22.00h. The observed variations may be related to: daily fluctuations of absorption or binding of the drug; diurnal variations of the hepatic drug metabolizing enzymes responsible for the inactivation; and/or diurnal variations in excretion rate of the drug.

Anticonvulsant Effects of Carbamazepine on Spontaneous Seizures in Rats with Kainate‐induced Epilepsy: Comparison of Intraperitoneal Injections with Drug‐in‐food Protocols

“…The plasma half‐life after IP injections and administrations of CBZ via gastric gavage are ∼3 h and ∼6 h, respectively (Carl and Smith, 1989; Honack and Loscher, 1989). Variability exists for the maintenance of CBZ levels related to the hour of administration (i.e., chronopharmacokinetics) and the subsequent measured half‐life (Bruguerolle et al, 1981). Previous reports suggested that CBZ (100 mg/kg) would need to be administered via oral gavage at least every 8 h during the day (Carl and Smith, 1989) and more frequently at night (Bruguerolle et al, 1981) to sustain therapeutic blood concentrations.…”

“…Variability exists for the maintenance of CBZ levels related to the hour of administration (i.e., chronopharmacokinetics) and the subsequent measured half‐life (Bruguerolle et al, 1981). Previous reports suggested that CBZ (100 mg/kg) would need to be administered via oral gavage at least every 8 h during the day (Carl and Smith, 1989) and more frequently at night (Bruguerolle et al, 1981) to sustain therapeutic blood concentrations. Chronic, repeated administration (i.e., weeks or months) of CBZ leads to autoinduction enzyme metabolism and its elimination half‐life is shortened by 50% (Eichelbaum et al, 1975; Frey and Loscher, 1980).…”

Carbamazepine affects water and electrolyte homoeostasis in rat--similarities and differences to vasopressin antagonism

“…At the chosen dosage of 50 mg/kg BW and with 2% tylose as a vehicle, CBZ was well tolerated and led to a plasma concentration of 14 μg/mL (measured 5 h after gavage, data not shown) which is in the therapeutical range in human treatment. Similar concentrations have been achieved in rat, and according to a previous study [20], we took into consideration the circadian pattern of CBZ pharmacokinetics with more sustained plasma concentrations when administered during the inactive phase.…”

Effects of Short-Term Treatment with Recombinant Human Growth Hormone on Carbamazepine Pharmacokinetics in Rats

“…Fat/muscle tissue ratio may be changed during rhGH treatment [10]. The plasma protein binding of CBZ is 60% to 80% in rats [36]. It is reported that rhGH can alter the amount and plasma concentrations of albumin in humans [37,38], depending on the dose and the duration of the growth hormone treatments.…”