Pharmacokinetics of piperine following single dose administration of benjakul formulation in healthy Thai subjects

Benjakul formulation is a Thai traditional medicine preparation, has also been used as an adaptogenic drug for cancer patients. No toxicity, either acutely or chronically has been reported in experimental animals and humans. The study was to preliminarily investigate the pharmacokinetics of piperine, the major active component of Benjakul formulation, following the administration of single oral doses of 100 (group 1) and 200 (group 2) mg Benjakul tablets in 20 healthy Thai subjects. Venous blood samples were collected before and after dosing. Serum concentrations of piperine were measured using HPLC-UV method. Pharmacokinetic analysis was performed by using model-independent analysis approach. Benjakul formulation was well tolerated in all subjects, with no apparent adverse events. Piperine was rapidly absorbed following the administration of both dosage levels.  The pharmacokinetics of piperine was dose–independent. The observed median first maximum concentration (Cmax-1st) of piperine of 1,078 ng/mL following the dose of 200 mg Benjakul was significantly higher than (p< 0.001) that of 100 mg dose (467 ng/mL). Median time to first maximum concentration (tmax-1st) was about 1 hours in both groups. The area under serum concentration-time curve (AUC 0-48hr) of 10,216 ng.hr/mL following 200 mg dose was also significantly greater than (p< 0.001) that of 100 mg dose (4,288 ng.hr/mL). It was noted however for the second maximum concentration (Cmax-2nd) of piperine at about 9 hours post-dosing observed in 9 (median: 203 ng/mL) and 7 (median: 499 ng/mL) subjects who received 100 and 200 mg Benjakul formulation, respectively.   Key words: Benjakul formulation, piperine, Piper chaba Hunter., Piper sarmentosum Roxb., Piper interruptum Opiz., Plumbago indica Linn., and Zingiber officinale Roscoe., pharmacokinetics.