RESEARCH/PRACTICE REPORTS CORRELATION OFDELAYED PEAK CONCENTRATION WITH INFUSION-SITE IRRITATION FOLWWING DIAZEPAM ADMINISTRATION

ABSTRACf: Diazepam 10 mg/2 mL iv was administered undiluted over five minutes to nine healthy men on two separate occasions. The infusion site was evaluated before and after each infusion by subject assessment of pain on a severity scale of zero (none) to ten (most). Blood samples were collected at 0,5,20,30,45, and 60 minutes, and periodically for 72 hours postinfusion. Diazepam plasma concentra-tions were determined by HPLC. Concentrations at five minutes (end of infusion) ranged from 0 to 889 ng/mL. Maximum plasma concentration (C....) was observed at 5 minutes for 10 treatments, at 20 minutes for 7 treatments, and at 30 minutes for I treatment. The observed C.... ranged from 221 to 889 ng/mL. When time to reach peak plasma concentration (t....) was 5 minutes, the C.... was significantly greater than when t.... was 20 minutes (670 ± 87 vs. 267 ± 40 ng/ml., p<O.OO5). The area under the curve did not differ significantly between these two groups. The pain score at the end o