Is rectally administered cisapride an effective prokinetic agent?

OBJECTIVE: To summarize the published data on the efficacy of rectally administered cisapride. DATA SOURCES: Published double-blind, placebo-controlled trials on rectally administered cisapride identified by MEDLINE (January 1966-December 1998) and International Pharmaceutical Abstracts (January 1970-December 1998) searches. DATA SYNTHESIS: Cisapride is an oral prokinetic agent that increases lower esophageal sphincter tone, accelerates gastric emptying, and increases small-bowel motility. Clinical trials of rectal cisapride have used both single- and multiple-dosing regimens. Typically, patients received one or two 30-mg suppositories (provided by the manufacturer). Rectal cisapride was effective in enhancing gastric emptying of solid or semisolid meals in healthy patients or patients with chronic gastric emptying disorders. Rectal cisapride was not effective in antagonizing the gastrointestinal effects of narcotic analgesics or promoting the return of small-bowel activity in adults with postoperative ileus. Mixed results were seen when rectal cisapride was used to promote enteral feedings in patients with persistent ileus. CONCLUSIONS: The use of rectal cisapride cannot be recommended at this time. Rectal cisapride was effective only in patients who could have otherwise taken either cisapride tablets or suspension but it was not effective in patients who are physically unable to swallow or restricted from ingesting anything orally following surgical procedures. Considering the varied patient populations and evaluation methods used in these studies, the lack of a commercially available cisapride suppository, and absence of studies involving extemporaneously prepared cisapride suppositories, the use of suppositories should be limited to investigational trials.

Determination of chlorpyrifos, chlorpyrifos oxon, and 3,5,6-trichloro-2-pyridinol in rat and human blood.

Analytical methods to quantitate chlorpyrifos and two potential metabolites, chlorpyrifos oxon (oxon) and 3,5,6-trichloro-2-pyridinol (TCP), in human and rat blood are described. Chlorpyrifos and the oxon were extracted simultaneously with a methanol/hexane mixture from 0.5 mL blood that was deactivated with an acidic salt solution. The extract was then concentrated and analyzed by negative-ion chemical ionization gas chromatography-mass spectrometry (NCI-GC-MS). TCP was extracted from a separate 0.1-mL aliquot of blood, also deactivated by the addition of acid. The t-butyldimethylsilyl derivative of TCP was formed using MTBSTFA, and the analysis was performed by NCI-GC-MS. Stable isotope analogues of chlorpyrifos (-13C2-15N), oxon (-13C2-15N), and TCP (-13C2) were used as internal standards. Oxon was observed to partially degrade to TCP during the sample analysis. Accurate oxon and TCP measurements were obtained with the use of oxon-13C2-15N, TCP-13C2, and TCP-13C2-15N internal standards, which compensated for both the degradation of oxon and the formation of artifactual TCP during analysis. The limits of quantitation were 1 ng/mL blood for both chlorpyrifos and oxon and 10 ng/mL for TCP. Calibration curves were linear over the concentration range of 2.5-2500 ng/mL solvent for chlorpyrifos and oxon and between 5 and 1060 ng/mL solvent for TCP. Taking concentration factors and extraction efficiencies into account, these linear ranges represent blood concentrations of approximately 0.3-300 ng/mL blood for chlorpyrifos and the oxon and 6-1300 ng/mL blood for TCP. The lowest spike level for chlorpyrifos and the oxon was 1 ng/mL blood, and the lowest spike level for TCP was 10 ng/mL blood. Recoveries from rat blood were as follows: 106-119% for chlorpyrifos, 94-104% for oxon, and 85-102% for TCP. In addition, chlorpyrifos and oxon were incubated with rat and human blood for various time intervals before deactivation to determine precautions that needed to be taken when collecting and handling specimens. No change in chlorpyrifos concentration was observed in rat blood up to 180 min at 37 degrees C. In contrast, the oxon was rapidly hydrolyzed to TCP in both rat (t 1/2 approximately 10 s) and human (t 1/2 approximately 55 s) blood held at 37 degrees C. The hydrolysis rate for the oxon was independent of whether a rat had been administered chlorpyrifos previously, the initial oxon concentration, the presence of chlorpyrifos, and the age or gender of the human volunteers. These results suggest rapid sample preparation is critical for accurate determinations of the oxon metabolite of chlorpyrifos. These methods provide excellent tools for use in chlorpyrifos pharmacokinetic modeling studies.

[Potentiometric measurements and skin surface acidity in health children and children with mucoviscidosis]. / Potentiometrische Messungen der Hautoberflächenazidität hautgesunder Kinder und von Kindern mit Mukoviszidose.

Actual acidity of the skin surface as well as the capacity to neutralize topically applied 0,01 n NaOH were measured by means of a potentiometric procedure. 50 children without diseases of their skin showed pH values between 4,5 and 6,1 (mean pH = 5,24) when tested at the volar forearms. A significant shift towards higher acidity became apparent by pH readings (4,1--5,7; mean 4,73) in 25 patients suffering from mucoviscidosis. In both groups no difference could be found in regeneration of the skin acidity after exposure to NaOH. Our results favour the assumption that elevated skin surface acidity in patients with mucoviscidosis is due to qualitative or quantitative differences in the biochemical composition of the epidermis.