| Abstrakt: |
Alterations to relevant pharmacokinetic processes by co-administered drugs are common phenomena of primary importance in drug treatment. These may impact therapeutic objectives positively or negatively; depending on whether the effects are desirable or not. The effect of methanol extract of the seeds of Aframomum melegueta (AMSE) on the pharmacokinetics of acetaminophen (N-acetyl-p-aminophenol; APAP) was investigated in Sprague-Dawley rats. Rats weighing 200-300 g were divided into two groups, baseline blood samples were taken, and rats in the test group were administered 25 mg/kg AMSE orally while the other group, serving as control, was administered normal saline (2 mL/kg). 30 minutes post-exposure, rats were administered 100 mg/kg APAP orally; blood samples were taken at times between 5 and 150 minutes, centrifuged, and APAP plasma concentrations were assayed using a colorimetric method for pharmacokinetic parameter determinations. AMSE resulted in an 83% reduction in the bioavailability of APAP. Relevant bioavailability indices such as Cmax (APAP+AMSE, 2.92±0.51 μg/mL; APAP, 15.6±4.9 μg/mL; P<0.05) and AUC (APAP+AMSE, 226±79.9; APAP, 1,320±405; P<0.05), were significantly reduced by AMSE. Although there was a slight improvement in the rate of APAP absorption in the presence of the AMSE (Tmax, 5 min) compared to its absence (Tmax, 15 min), bioavailability in the presence of AMSE was only 17% (F, 0.17) of the control value. Results showed the ability of the extract of the seeds to severely reduce the bioavailability of APAP. The factors responsible for this drastic effect are not known, but interactions between APAP and Nitric oxide (NO) signaling molecules cannot be ruled out. [ABSTRACT FROM AUTHOR] |
