#Winnonlin license cost trial
The drug also has shown efficacy and tolerability in a phase II clinical trial for epilepsy patients, and three phase III clinical trials have been completed for treatment in partial seizures. In phase I clinical trials to healthy subjects, carisbamate has shown linear pharmacokinetics at doses of 100 to 1,500 mg, high oral bioavailability (F) of > 95% and a low oral clearance (CL/F) of 3.4–4.2 L/h, equaling < 5% of liver blood flow. Although the exact mechanism of action for carisbamate is not known, carisbamate has been studied for the treatment of epilepsy, essential tremor and migraine. This PBPK model developed from the preclinical data for carisbamate would be useful for predicting the PK of carisbamate in various clinical settings.Ĭarisbamate (S-2-O-carbamoyl-1-o-chlorophenyl-ethanol) is an investigational neuromodulatory agent, initially developed from SK Biopharmaceuticals (Seongnam, Korea) for antiepileptic treatment. The human PK parameters and profiles predicted from the validated PBPK model were similar to the clinical data. The human PK of carisbamate after oral dosing of 750 mg was simulated by using this validated PBPK model. The PBPK model was optimized and validated by using the in vitro and in vivo data.
Based on these study results, human pharmacokinetic (PK) profile has been predicted using physiologically based pharmacokinetic (PBPK) modeling. Preclinical in vitro and in vivo studies of carisbamate have been studied through the developed bioanalytical method. A quadratic regression (weighted 1/concentration 2), with an equation y = ax 2 + bx + c, was used to fit calibration curves over the concentration range from 9.05 to 6,600 ng/mL for carisbamate in rat plasma.
In this study, a liquid chromatography-quadrupole time-of-flight mass spectrometric (LC-qTOF-MS) method was developed and applied for the determination of carisbamate in rat plasma to support in vitro and in vivo studies. Carisbamate is an antiepileptic drug and it also has broad neuroprotective activity and anticonvulsant reaction.
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