Influence of menstrual cycle on the pharmacokinetics of paracetamol through salivary compartment in healthy subjects

Hormonal changes during the different phases of menstrual cycle may influence drug disposition. The objective of this study was to investigate the influence of the menstrual cycle on the pharmacokinetics of paracetamol through salivary compartment in young healthy Indian women (n = 12) with regular menstrual cycles. The subjects received an oral dose of 1 g paracetamol on the 3rd, 13th, and 23rd days of their menstrual cycle in a 3 x 3 randomized crossover design. Saliva samples were collected at predetermined time intervals and the paracetamol content in them was estimated using an established HPLC method. The pharmacokinetics of paracetamol was worked out using a model-independent method employing WinNonlin 3.1. The mean Cmax of paracetamol was significantly (p < 0.05) lower (31.5%) in the ovulatory phase than in the follicular phase. The mean AUC0-t and AUC0-infinity values were significantly (p < 0.05) lower in the ovulatory phase than those in the luteal phase. These changes could be due to increased first-pass metabolism and decreased bioavailability of paracetamol during the ovulatory phase.