Noninferiority clinical trial comparing the bowel cleansing efficacy of sodium phosphate tablets (Quiklean®) with a polyethylene glycol/bisacodyl kit.

BACKGROUND: Efficient bowel cleansing is essential for a successful colonoscopy, but the ideal cleansing agent, volume, and pharmaceutical dosage form have yet to be determined. Small-volume cleansers enhance patient compliance. AIM: To compare the bowel cleansing efficacy of 32-tablet sodium phosphate (Quiklean®) with 2-L polyethylene glycol (PEG)/bisacodyl (Klean-Prep/ Dulcolax®) under identical dietary recommendations. METHODS: This multicenter, randomized, parallel-group, noninferiority clinical trial enrolled 472 outpatients, randomized 456 subjects, and scheduled 442 subjects to undergo colonoscopy (Quiklean® = 222 and Klean-Prep/Dulcolax® = 220). After bowel preparation, a colonoscopist performed the colonoscopy with video recorded for rating. The primary efficacy endpoint was the bowel cleansing quality using the Aronchick Scale. The secondary endpoints were the bowel cleansing efficacy of three colon segments, tolerability and acceptability, safety using the Ottawa bowel preparation scale, questionnaires by subjects, and monitoring of adverse events. RESULTS: Success rates (Excellent + Good) of the bowel cleansing quality by Aronchick Scale were 98.6% (n = 205) and 97.6% (n = 204) in the Quiklean® and Klean-Prep/Dulcolax® groups, respectively. Quiklean® demonstrated noninferiority over Klean-Prep/Dulcolax® in colon cleansing efficacy. Quicken showed better tolerability and acceptability in the overall experience (was rated as excellent; 24.0% vs 17.2%; P = 0.0016) and the taste of the study preparation (was rated as excellent, 23.1% vs 13.4%; P < 0.0001) than Klean-Prep/Dulcolax®. Safety profiles did not differ between the two groups. Our data indicate that Quiklean® is an adequate, well-tolerated bowel cleansing preparation compared with the standard comparator Klean-Prep/Dulcolax®. CONCLUSION: Quiklean® is sodium phosphate tablets available on Taiwan's market for bowel preparation; it potentially offers patients an alternative to standard large-volume bowel preparation regimens and may, therefore, increase positive attitudes toward colonoscopies and participation rates.

Increased Systemic Exposure of Methotrexate by a Polyphenol-Rich Herb via Modulation on Efflux Transporters Multidrug Resistance-Associated Protein 2 and Breast Cancer Resistance Protein.

Scutellariae radix (SR, roots of Scutellaria baicalensis Georgi), a popular Chinese medicine, contains plenty of flavonoids such as baicalin, wogonoside, baicalein, and wogonin. Methotrexate (MTX), an important immunosuppressant with a narrow therapeutic index, is a substrate of multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP). This study investigated the effect of SR on MTX pharmacokinetics and the underlying mechanisms. Rats were orally administered MTX alone and with 1.0 or 2.0 g/kg of SR. The serum concentrations of MTX were determined by a fluorescence polarization immunoassay. Cell models were used to explore the involvement of MRP2 and BCRP in the interaction. The results showed that 1.0 g/kg of SR significantly increased Cmax, AUC(0-30), AUC(0-2880), and mean residence time (MRT) of MTX by 50%, 45%, 501%, and 347%, respectively, and 2.0 g/kg of SR significantly enhanced the AUC(0-2880) and MRT by 242% and 293%, respectively, but decreased AUC(0-30) by 41%. Cell line studies indicated that SR activated the BCRP-mediated efflux transport, whereas the serum metabolites of SR inhibited both the BCRP- and MRP2-mediated efflux transports. In conclusion, SR ingestion increased the systemic exposure and MRT of MTX via modulation on MRP2 and BCRP.

Rhubarb decreased the systemic exposure of cyclosporine, a probe substrate of P-glycoprotein and CYP 3A.

1. Rhubarb, rhizome of Rheum palmatum L. (RP), is an important herb in clinical Chinese medicine. 2. Cyclosporine (CSP) is an immunosuppressant with narrow therapeutic window. The oral bioavailability of CSP was associated with P-glycoprotein (P-gp) and CYP 3A4. CSP was used as a probe substrate to investigate the in vivo modulation effects of RP on P-gp and CYP 3A. 3. Rats were orally administered 2.5 mg/kg of CSP with and without 0.25 and 1.0 g/kg of RP. The blood CSP concentration was determined by a specific monoclonal fluorescence polarization immunoassay. 4. Both dosages of RP significantly decreased the Cmax and AUC0-t of CSP in rats. Mechanism studies indicated that RP activated the functions of P-gp and CYP 3A. 5. RP ingestion reduced the systemic exposure of CSP through activating P-gp and CYP 3A.