Optimizing metoclopramide control of cisplatin-induced emesis.

Using an original high-pressure liquid chromatographic assay, we measured serum levels of metoclopramide and defined a concentration-response relationship for metoclopramide control of cisplatin-induced emesis. Using a metoclopramide regimen of 2 mg/kg body weight intravenously every 2 hours for four doses, we found that serum levels greater than 850 ng/mL immediately before the third dose were associated with complete control of emesis (less than three episodes) in 78% of patients and partial control (three to five episodes) in 18%. No patient with levels less than 850 ng/mL had complete control of emesis; only 42% had partial control (p less than 0.001). Increases in dosage for patients with low levels and poor responses improved control in four of five patients. Elderly patients had drug levels similar to those of young patients but had fewer episodes of emesis (p = 0.044), suggesting that elderly patients have increased sensitivity to this drug. The metoclopramide dose can be raised up to 2.75 mg/kg with an improvement in emetic control in patients who have an inadequate response to doses of 2 mg/kg and no toxicity.

Effect of storage at specified temperature and humidity on properties of three directly compressible tablet formulations.

Direct compression tablets containing sodium starch glycolate, an alginate derivative, or povidone as a disintegrant, magnesium stearate as a lubricant, amaranth as a tracer, and dibasic calcium phosphate dihydrate as the matrix were stored for 30 days at 23 degrees and 75% relative humidity (R.H.), 45 degrees and 75% R.H., and 65 degrees and 40% R.H. Samples were evaluated after 0, 10, 20, and 30 days for size, hardness, and dissolution characteristics. Although no significant changes in the dimensions or hardness of the three tablet formulations, prepared at three different compaction pressures, were observed, the dissolution efficiency of the systems showed significant changes, some systems dissolving more rapidly and some more slowly after storage. In some cases, the changes were so substantial as to indicate the possibility of significant changes of the bioavailability of drugs formulated in such systems. The relevance of this work to the problem of evaluating aging effects on the physical properties of tablets is discussed.