Determination of temporal changes in hepatic drug-oxidizing capacity using plasma metabolite/caffeine ratios in non-pregnant and pregnant goats.

Caffeine (CF) is a metabolic probe drug used in the determination of the hepatic drug-oxidizing capacity. The aim of this study was to investigate temporal changes in the hepatic drug-oxidizing capacity using plasma metabolite/CF ratios in non-pregnant goats (n = 11) and pregnant goats (n = 23). CF (5 mg/kg, intravenous) was administered in six periods (Period 1-6) with 45 days between two periods. The plasma levels of CF and its metabolites, theophylline (TP), theobromine (TB) and paraxanthine (PX), were determined by HPLC-UV. To evaluate hepatic drug-oxidizing capacity in terms of enzymes that play a role in CF metabolism, the plasma metabolic ratios including TB/CF, PX/CF, TP/CF and TB + PX + TP/CF were determined at 10 h following CF administration. Plasma metabolite/CF ratios were similar between non-pregnant and pregnant goats. However, plasma metabolite/CF ratios in Period 3 (45 days in pregnant goats) were significantly higher than those other periods in both pregnant and non-pregnant goats. The effect of pregnancy may not be observed on drugs that are substrates of enzymes involved in CF metabolism in goats.