1 To investigate the effect of cimetidine on the pharmacokinetics of R(-)-and S(+)-ibuprofen, six healthy male volunteers received orally 800 mg racemic ibuprofen both in the drug-free state (control phase, C) and on the second day of a 3 day course of oral cimetidine, 1 g daily (treatment phase, T). The two phases (14 days apart) were randomised in a balanced cross-over manner.2 The plasma concentrations of R(-)-and S(+)-ibuprofen were measured by highperformance liquid chromatography (h.p.l.c.). The protein binding of the enantiomers was assessed in a selection of plasma samples from each volunteer. Following alkaline hydrolysis of glucuronide conjugates, the urinary recoveries of ibuprofen and its major metabolites were measured by h.p.l.c. 3 There was no difference (P > 0.05, two-tailed Student's t-test; data expressed as mean ± s.d.) between C and T phases in the total area under the plasma concentration-time curve of R(-)-ibuprofen (C 4514 ± 1063 mg 1-1 min vs T 4665 ± 1435 mg 1-1 min) and S(+)-ibuprofen (C 6460 ± 1063 mg 1-1 min vs T 6886 ± 1207 mg 1-1 min). Similarly, for each enantiomer, there was no difference between the two phases in the terminal half-life, the maximum plasma concentration or the time of its occurrence. 4 Cimetidine treatment had no effect (P > 0.05) on the time-averaged percent unbound in plasma of R(-)-ibuprofen (C 0.419 ± 0.051% vs T 0.435 ± 0.060%) and S(+)-ibuprofen (C 0.643 ± 0.093% vs T 0.633 ± 0.053%). 5 There was no difference (P > 0.05) in the percentage of the administered dose recovered in the urine as ibuprofen plus metabolites (C 84.9 ± 7.3% vs T 87.6 ± 3.9%). 6 The results indicate that the pharmacokinetics of R(-)-and S(+)-ibuprofen after a single oral dose of racemic ibuprofen were not influenced by concurrent cimetidine administration.

Currently, a number of in vitro methods are in use worldwide to assess arsenic (As) bioaccessibility in soils. However, a dearth of research has been undertaken to compare the efficacy of the in vitro methods for estimating in vivo relative As bioavailability. In this study, As bioaccessibility in contaminated soils (n = 12) was assessed using four in vitro assays (SBRC, IVG, PBET, DIN). In vitro results were compared to in vivo relative As bioavailability data (swine assay) to ascertain which methodologies best correlate with in vivo data. Arsenic bioaccessibility in contaminated soils varied depending on the in vitro method employed. For the SBRC and IVG methods, As bioaccessibility generally decreased when gastric-phase values were compared to the intestinal phase. In contrast, extending the PBET and DIN assays from the gastric to the intestinal phase resulted in an increase in As bioaccessibility for some soils tested. Comparison of in vitro and in vivo results demonstrated that the in vitro assay encompassing the SBRC gastric phase provided the best prediction of in vivo relative As bioavailability (R(2) = 0.75, Pearson correlation = 0.87). However, relative As bioavailability could also be predicted using gastric or intestinal phases of IVG, PBET, and DIN assays but with varying degrees of confidence (R(2) = 0.53-0.67, Pearson correlation = 0.73-0.82).

BackgroundMillions of people worldwide consume arsenic-contaminated rice; however, little is known about the uptake and bioavailability of arsenic species after arsenic-contaminated rice ingestion.ObjectivesIn this study, we assessed arsenic speciation in greenhouse-grown and supermarket-bought rice, and determined arsenic bioavailability in cooked rice using an in vivo swine model.ResultsIn supermarket-bought rice, arsenic was present entirely in the inorganic form compared to greenhouse-grown rice (using irrigation water contaminated with sodium arsenate), where most (~ 86%) arsenic was present as dimethylarsinic acid (organic arsenic). Because of the low absolute bioavailability of dimethylarsinic acid and the high proportion of dimethylarsinic acid in greenhouse-grown rice, only 33 ± 3% (mean ± SD) of the total rice-bound arsenic was bioavailable. Conversely, in supermarket-bought rice cooked in water contaminated with sodium arsenate, arsenic was present entirely in the inorganic form, and bioavailability was high (89 ± 9%).ConclusionsThese results indicate that arsenic bioavailability in rice is highly dependent on arsenic speciation, which in turn can vary depending on rice cultivar, arsenic in irrigation water, and the presence and nature of arsenic speciation in cooking water. Arsenic speciation and bioavailability are therefore critical parameters for reducing uncertainties when estimating exposure from the consumption of rice grown and cooked using arsenic-contaminated water.

No abstract