Certain commonly occurring single-nucleotide polymorphisms in OATP-C, such as T521C (Val174Ala), are likely to be associated with altered pharmacokinetics of pravastatin. Large clinical studies are needed to confirm these observations.

When baicalin was orally administered to conventional rats, it was detected in their plasma for 24 h after administration, but baicalein, the aglycone of baicalin, was not detected. However, when baicalin was given to germ-free rats, only a small amount of baicalin was detected in their plasma within 2 h after the administration, its AUC0-lim (the area under the concentration-time curve from 0 to last determination time) being 12.0% of that in conventional rats. Subsequently, a considerable amount (55.1 +/- 6.2%) of baicalin was recovered from the gastrointestinal tract even 4 h after administration. When baicalein was orally administered to conventional rats, however, baicalin appeared rapidly in their plasma at an AUC0-lim value similar to that obtained after oral administration of baicalin, despite the absence of baicalein in plasma. When intestinal absorption was evaluated by the rat jejunal loop method, baicalein was absorbed readily, but only traces of baicalin were absorbed. Moreover, in conventional rats a small amount (13.4 +/- 3.1%) of baicalin and an appreciable amount (21.9 +/- 3.4%) of baicalein were recovered from the gastrointestinal tract even 4 h after oral administration of baicalin, but only a small amount (3.93 +/- 1.43%) of baicalein was detected in the intestinal tract 1 h after administration of baicalein. Baicalin was transformed to baicalein readily by the rat gastric and caecal contents. When baicalin was administered orally to conventional rats, an appreciable amount of baicalein was recovered in their gastrointestinal tracts. Moreover, baicalein was efficiently conjugated to baicalin in rat intestinal and hepatic microsomes. These results indicate that baicalin itself is poorly absorbed from the rat gut, but is hydrolysed to baicalein by intestinal bacteria and then restored to its original form from the absorbed baicalein in the body.

No abstract

Analysis of linear polarization data obtained by the Pioneer Venus Orbiter Cloud Photopolarimeter experiment indicates that the visible clouds at low and mid‐latitudes are composed predominantly of 1 µm radius H2SO4 droplets, an identification made previously by using earth‐based observations. Mixed within and extending above this main visible cloud is an extensive haze of submicron‐sized particles. These haze particles have a refractive index of 1.45±0.04 at λ ≃550 nm, an effective radius of 0.23±0.04 µm, and a size distribution with an effective variance of 0.18±0.1. The polarization of the bright regions poleward of about 55° latitude is produced almost entirely by this submicron haze. The submicron haze has been found to exhibit large spatial and temporal variations. In January 1979 the haze vertical optical thickness in the polar region at λ=365 nm was τh ∼0.8 above the main cloud of l‐µm particles. By comparison, the optical thickness of the haze above the main cloud at low latitudes was typically 1 order of magnitude smaller, τh ∼0.06, however haze mixed within the cloud contributed ∼18% of the total scattering cross section per unit volume at λ=365 nm. More recent observations indicate that there are major changes of the haze on time scales of hundreds of days (e.g., the optical thickness of the polar cap haze is smaller by a factor of 2–3 in October 1979 than in January 1979). Substantial diurnal variations exist at low latitudes, with a greater amount of haze near the morning terminator than near the noon meridian. The global distribution of haze will be monitored during the extended Pioneer Venus mission to permit analysis of long time scale variations as well as correlation with characteristics of the atmospheric dynamics deduced from ultraviolet images of the cloud tops.

Two fast and sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS)-based bioanalytical assays were developed and validated to quantify the active and three inactive metabolites of prasugrel. Prasugrel is a novel thienopyridine prodrug that is metabolized to the pharmacologically active metabolite in addition to three inactive metabolites, which directly relate to the formation and elimination of the active metabolite. After extraction and separation, the analytes were detected and quantified using a triple quadrupole mass spectrometer using positive electrospray ionization. The validated concentration range for the inactive metabolites assay was from 1 to 500 ng/mL for each of the three analytes. Additionally, a 5x dilution factor was validated. The interday accuracy ranged from -10.5% to 12.5% and the precision ranged from 2.4% to 6.6% for all three analytes. All results showed accuracy and precision within +/-20% at the lower limit of quantification and +/-15% at other levels. The validated concentration range for the active metabolite assay was from 0.5 to 250 ng/mL. Additionally, a 10x dilution factor was validated. The interbatch accuracy ranged from -7.00% to 5.98%, while the precision ranged from 0.98% to 3.39%. Derivatization of the active metabolite in blood with 2-bromo-3'-methoxyacetophenone immediately after collection was essential to ensure the stability of the metabolite during sample processing and storage. These methods have been applied to determine the concentrations of the active and inactive metabolites of prasugrel in human plasma.