No abstract

Organic anion transporting polypeptides (OATPs) 1B are drug transporters mainly expressed in the sinusoidal membrane. In previous reports, genetic factor, 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid (CMPF), which is one of the uremic toxins, inflammatory cytokines such as tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) decreased OATP1B1 activity in vitro, but in vivo effects of these factors have not been elucidated. Plasma coproporphyrin‐I (CP‐I) is spotlighted as a highly accurate endogenous substrate of OATP1B. This study focused on patients with rheumatoid arthritis (RA) and evaluated the influence of several factors comprising gene polymorphisms, uremic toxins, and inflammatory cytokines on OATP1B activity using plasma CP‐I concentration. Thirty‐seven outpatients with RA who satisfied the selection criteria were analyzed at the time of recruitment (baseline) and at the next visit. OATP1B1*15 carriers tended to have higher CP‐I concentration compared with noncarriers. Plasma CP‐I correlated positively with CMPF concentration, but did not correlate with IL‐6 or TNF‐α concentration. Multiple logistic regression analysis by stepwise selection identified plasma CMPF concentration and OATP1B1*15 allele as significant factors independently affecting plasma CP‐I concentration at baseline and at the next visit, respectively. In conclusion, the present results suggest that inflammatory cytokines do not have clinically significant effects on OATP1B activity, whereas the effects of genetic polymorphisms and uremic toxins should be considered.

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No abstract

Pilocarpine increases the release of salivary substance P and CGRP-IS. This suggests that one mechanism by which pilocarpine improves dry mouth is by local stimulation of neuropeptidergic nerves. Moreover, saliva levels of substance P showed good correlation with the plasma levels. The substance P levels in saliva and plasma may be good indicators of the effects of drugs used in dry mouth/xerostomic patients.