The effect of antacid and cimetidine on the oral absorption of the antifungal agent SCH 39304.

The single-dose pharmacokinetics of the antifungal agent SCH 39304 (Schering-Plough Corp., Kenilworth, NJ) were assessed alone and in combination with antacid and cimetidine. On three separate occasions nine healthy men received a single oral 50 mg dose of SCH 39304 either alone, with 60 mL antacid, or with oral cimetidine 300 mg four times a day for 4 days. Concomitant antacid or cimetidine administration had no significant effect on any of the SCH 39304 pharmacokinetic parameters studied. The oral absorption of SCH 39304, as assessed by the area under the plasma concentration-time curve (AUC) and the amount of drug recovered unchanged in the urine, was not affected by either antacid or cimetidine. The AUC0-1 for the drug given alone was 80.5 +/- 15.8 micrograms.hr/mL, compared to 81.4 +/- 12.7 and 79.7 +/- 9.6 micrograms.hr/mL with concomitant antacid and cimetidine, respectively. The amount of drug excreted in the urine (Ae0-1) was 22.7 +/- 5.1, 24.2 +/- 9.2, and 23.6 +/- 7.6 mg when the drug was given alone, with antacid, and with cimetidine, respectively. Antacid coadministration delayed absorption as evidenced by an increase in the tmax in 7 out of 9 subjects, although this did not reach statistical significance (P = .082, Wilcoxon test). We conclude that concomitant antacid or cimetidine does not alter the oral absorption or pharmacokinetic disposition of single-dose SCH 39304.

Pharmacokinetics and bioavailability of dilevalol in normotensive volunteers.

The bioavailability and pharmacokinetics of dilevalol following oral and intravenous administration were investigated in 12 healthy male volunteers. Dilevalol HCl was administered as a 200-mg oral tablet and a 50-mg intravenous infusion using a randomized cross-over design. Blood and urine samples were collected over 60 hours and analyzed for unchanged and total (unchanged plus Glusulase-released) dilevalol using a high performance liquid chromatography (HPLC) assay. After intravenous administration, total body clearance and volume of distribution of unchanged dilevalol were determined to be 23.2 mL/min/kg and 24.6 L/kg, respectively. After oral administration, a mean maximum concentration of 62 ng/mL was reached at an average peak time of 1.4 hours. Drug was eliminated with a half-life of 8.3 hours after oral administration and 12 hours after intravenous administration. Based on plasma levels and urinary excretion of total dilevalol, the drug was completely absorbed; however, due to first-pass metabolism, the absolute bioavailability of unchanged drug was 11 to 14%.

Stability and visual compatibility of bretylium tosylate with selected large-volume parenterals and additives.

The stability of bretylium tosylate when mixed with large-volume parenteral (LVP) solutions was assessed over a four-week period, and the compatibility of bretylium tosylate when mixed with eight frequently used drugs was evaluated. Bretylium tosylate admixtures of approximately 1 mg/ml were prepared in both polyvinyl chloride (PVC) bags and glass bottles of 5% dextrose injection, 0.9% sodium chloride injection, and lactated Ringer's injection. The admixtures were examined visually and stored for four weeks at 25 +/- 0.5 degree C under fluorescent light. The concentrations of bretylium tosylate were determined spectrophotometrically at times 0.25, 0.5, 1, 3, 8, 24, and 48 hours and twice weekly thereafter for four weeks. Spectrophotometric assays were confirmed with high-pressure liquid chromatography. Admixtures of bretylium tosylate were prepared with aminophylline, calcium gluconate, digoxin, regular insulin, lidocaine hydrochloride, phenytoin sodium, procainamide hydrochloride, and quinidine gluconate in 5% dextrose injection and 0.9% sodium chloride injection. The admixtures were examined visually for 48 hours. The concentration of bretylium tosylate did not change appreciably during the four-week study period. There were no signs of haze, precipitation, color change, or evolution of gas. There were no apparent differences in stability when comparing the glass with the PVC containers. Bretylium tosylate was also found to be compatible with all the additives tested except phenytoin sodium; a precipitate formed immediately when the latter drug was added to the bretylium tosylate solution. Bretylium tosylate was stable for four weeks in the LVP solutions studied in both glass and PVC containers. The admixtures of bretylium sodium with the other drugs were all visually compatible except those containing phenytoin sodium.

Stability of dobutamine hydrochloride in selected large-volume parenterals.

Stability of dobutamine hydrochloride when mixed with large-volume parenteral solutions was assessed. Dobutamine hydrochloride was added to large-volume solutions of 5% dextrose injection, 0.9% sodium chloride injection, lactated Ringer's injection, and 5% dextrose and 0.45% sodium chloride injection, in both glass and polyvinyl chloride containers; the initial concentration was 1 mg/ml. After 0.25, 1, 3, 8, 24, and 48 hours, the concentration of dobutamine hydrochloride was determined by high-pressure liquid chromatography assay, and each solution was visually examined for evidence of haze, precipitation, color change, or evolution of gas. Concentration of dobutamine hydrochloride in the samples did not exhibit any appreciable change over the 48-hour period, and no HPLC peaks indicating degradation products were noted. Color changes were observed in some of the solutions, but no other visual changes occurred. There were no apparent differences in stability between the admixtures packaged in glass and those in polyvinyl chloride bags. At the concentration studied, dobutamine hydrochloride is stable in the admixtures tested for a minimum of 48 hours.

Stability and compatibility of lidocaine hydrochloride with selected large-volume parenterals and drug additives.

The stability of lidocaine hydrochloride in six commonly used large-volume parenterals when stored for 14 days and the visual compatibility of lidocaine hydrochloride in admixtures with eight frequently used drugs were studied. Lidocaine hydrochloride admixtures of 2 mg/ml were prepared in both glass and plastic containers of 5% dextrose injection, 0.9% sodium chloride injection, lactated Ringer's injection, 5% dextrose and lactated Ringer's injection, 0.45% sodium chloride injection (plastic container only), and 0.45% sodium chloride and 5% dextrose injection. The admixtures were examined visually and stored for 14 days at 25 +/- 0.5 degrees C under fluorescent light. Lidocaine hydrochloride concentrations were determined spectrophotometrically at times 0, 0.25, 1, 3, 8, and 24 hours, and at 24-hour intervals thereafter. Spectrophotometric assays were confirmed with high-pressure liquid chromatography. Admixtures of lidocaine hydrochloride were prepared with aminophylline, bretylium tosylate, calcium gluconate, digoxin, dopamine hydrochloride, regular insulin, phenytoin sodium, and procainamide hydrochloride in 5% dextrose injection, 0.9% sodium chloride injection, and lactated Ringer's injection. The admixtures were examined visually for 24 hours. Admixtures of lidocaine hydrochloride were stable for 14 days. All admixtures of lidocaine hydrochloride with other drugs were visually compatible except those containing phenytoin sodium. It is concluded that lidocaine hydrochloride is stable in the solutions studied for 14 days at 25 degrees C and visually compatible for 24 hours in admixtures containing all drugs studied except phenytoin sodium.