Phase I evaluation of zalcitabine administered to human immunodeficiency virus-infected children.

The safety, tolerability, and pharmacokinetics of zalcitabine (ddC) in a single oral dose (0.02 mg/kg) was evaluated in 23 mildly symptomatic human immunodeficiency virus-infected children (mean age, 4.2 years). After administration of ddC, blood samples were obtained at 0.5, 1, 1.5, 2, 4, 6, and 8 h for analysis. The drug was well tolerated and no side effects were noted. Plasma ddC levels were determined by ion spray liquid chromatography/tandem mass spectrometry. ddC was rapidly absorbed, with a mean maximum plasma concentration of 9.3 ng/mL (range, 3.2-14.1) attained within a mean of 1 h (range, 0.5-2.0). Mean elimination half-life was 1.4 h (range, 1.0-3.5), mean area under the plasma concentration-time curve was 25 ng.h/mL (range, 11-37), and mean total body clearance was 14.6 mL/min/kg (range, 8.9-30.6). Plasma concentrations were lower and the half-life shorter in these children than in adults given comparable doses, suggesting that ddC may be cleared more rapidly in children than adults.

Drug release rates from four sizes of a new transdermal nitroglycerin adhesive patch.

This study was conducted to determine the amount of nitroglycerin released from transdermal nitroglycerin patches of four different sizes: 3.3 cm2, 6.7 cm2, 13.3 cm2, and 20 cm2. Thirty healthy men received a single 24-hour application of each patch size according to a randomized, open-label, four-period crossover design. A 24-hour interval separated each treatment period. The total amount of nitroglycerin released by the four patches was proportional to size. All four patch sizes released nitroglycerin at a comparable rate. The mean overall 24-hour release rate of 0.76 mg/cm2 was similar to the release rate of 0.75 mg/cm2/24 hr observed in a previous study. Adverse experiences common to nitroglycerin administration were reported for all patch sizes, with headache, light-headedness, and nausea reported most frequently.

Performance of a new transdermal nitroglycerin adhesive patch formulation.

This two-period crossover study in 24 healthy men compared the transdermal absorption of nitroglycerin from a new 20-cm2 nitroglycerin adhesive transdermal patch applied for a single 24-hour period (q24hr) with that from one inch of 2% nitroglycerin ointment applied over a 50-cm2 area every eight hours (q8hr) during a single 24-hour period. The observed differences in pharmacokinetic parameters were expected, based on product design (q24hr vs q8hr) and surface area (20 cm2 vs 50 cm2); however, when corrected for surface area, the mean plasma AUC ratios indicated that the patch delivered about 1.5 times more drug than the ointment. The patch delivery of nitroglycerin was confirmed by patch residual results, which indicated nitroglycerin was released at a rate of 0.75 mg/cm2/24 hrs. The patch exhibited good skin adhesion throughout the 24-hour application period.