The plasma concentrations of repaglinide in 16 male subjects were determined after an oral dose of 4 mg. Two-peak concentrations in plasma were observed. A type of one-compartment model with double sites of drug absorption was developed and successfully used to fit the data. A good agreement between observed and predicted data was found in all subjects with correlation index r2 > 0.97. The corresponding pharmacokinetic parameters were estimated as follows: Tmax1 0.61 +/- 0.14 h, Tmax2 1.45 +/- 0.43 h, Cmax1 40.60 +/- 20.57 ng/ml, Cmax2 42.70 +/- 17.54 ng/ml, T1 0.12 +/- 0.07 h, T2 0.67 +/- 0.30 h and T3 1.03 +/- 0.35 h.

Cefixime (CFX) absorption kinetics after oral administration to humans was studied. Four distinct models, incorporating a delay of absorption and first-order elimination kinetics, i.e. first-order absorption (M1), zero-order absorption (M0), Michaelis-Menten type absorption (MM) and Michaelis-Menten type absorption with 'an absorption window' (MM-delta t) were used to fit concentration data of CFX in 10 Chinese men following an oral dose of 400 mg. r2 and AIC were selected as measures of goodness-of-fit. The results show that the MM-delta t model provided a better fit than the other three models. The kinetic parameters were estimated as follows: Vmax' = 10.80 +/- 3.80 mg.l-1.h-1; K(m)' = 88.31 +/- 2.75 micrograms.ml-1; delta t = 4.75 +/- 0.85 h; T1/2 = 4.20 +/- 0.92 h; Tmax = 5.20 +/- 0.92 h; and Cmax = 6.04 +/- 1.70 mg.l-1.

Effect of erythromycin (ERY) on oral absorption of nimodipine (NMD) in female and male rat was investigated in vivo and in vitro. In vivo, at 15 min following oral dose of 50 mg/kg ERY, an oral dose 20 mg/kg NMD was given to rats, plasma concentrations of NMD were determined. In vitro, everted jejunum sac and ileum sac were used, NMD transport from mucosal side to serol side was measured, in absences of ERY and cyclosprin A (CSA) or in presence of ERY and CSA. Large gender difference was found after oral dose NDM. Male rats had lower plasma concentration than female rat did. AUC180 and Cmax in male rats were less than 5-folds and 3-folds than those in female rats, respectively. Co-administrating ERY may increase plasma concentrations of NMD in rats. AUC180 in male rats and female rats were 2.2-folds and 1.9-folds of those NMD alone, respectively. Cmax was about 3-folds of that NMD alone. The NMD transport in intestine showed a regional variation and gender differences. In female rat, transport rate in the jejunum was about 1.3 higher than ileum. Both ERY and CSA significant increases transport of NMD. Contrast to female, NMD transport in jejunum was lower that that in ileum. Bothe ERY and CSA had little effect on NMD transport in intestine. These results indicated that there existed gender difference in oral absorption of NMD and effect of ERY on oral absorption kinetics of NMD in female rats was different from that in male rat.

1. The aim of the current study was to investigate the characteristics of biliary excretion of antofloxacin (ATFX) in rats. Rats received a bolus intravenous injection followed by a constant-rate infusion of ATFX. When plasma concentrations of ATFX reached steady state, cyclosporin A, erythromycin, probenecid, cimetidine and diclofenac were administered intravenously to the rats. Samples of blood and bile were collected and the concentrations of ATFX were measured and the corresponding pharmacokinetic parameters were estimated. 2. Biliary excretion of ATFX was observed in rats subjected to CCl(4)-induced experimental hepatic injury for 24 h (CCl(4)-EHI(24h)). Steady state concentrations of ATFX were attained at 60 min following infusion. 3. A slight increase in concentration of ATFX in plasma was observed after cyclosporin A, erythromycin, probenecid and cimetidine treatment. Significant increases in ATFX plasma levels were found in rats treated with diclofenac. Cyclosporin A, erythromycin, probenecid, cimetidine and diclofenac treatment significantly decreased the steady state biliary clearance of ATFX to 55, 68, 54, 53 and 56% of control values, respectively. 4. Cyclosprin A, probenecid, erythromycin and cimetidine also inhibited the biliary excretion of ATFX glucuronide. Significant decrease in the steady state biliary clearance of ATFX and its glucuronide was observed in CCl(4)-EHI(24h) rats. 5. These results indicate that multiple transporters are possibly involved in the biliary excretion of ATFX.

In the present study, the pharmacokinetics of limonin (LM) were investigated in male and female rats. LM concentrations in the plasma were determined after the oral administration of 36 mg/kg LM or after intravenous (i.v.) injection of LM 3.6 mg/kg respectively. Concentrations in the tissues, urine, feces and bile were also analyzed following the oral administration of 36 mg/kg of the test product. It was found that the plasma concentrations of LM in female rats were significantly higher (P < 0.01) than those in male rats. Assessment of the effects of limonin based on the C(max) and AUC in female rats showed that levels were about 50-fold higher than those in male rats after oral administration of 36 mg/kg LM. Furthermore, after i.v. administration of 3.6 mg/kg LM, the C(max) and AUC in female rats was found to be about 3-fold higher than those in male rats. The total excretion of LM in the urine and bile of female rats was also found to be significantly higher than in male rats, which displayed lower concentrations of LM in the tissues, amounting to around one-half to one-tenth of those in female rats, apart from levels in the rectum and duodenum. In conclusion, the present results demonstrate the existence of marked gender difference in LM pharmacokinetics in rats.