Oregon Poison Center, Portland, OR 97210, USA.
J Med Toxicol. 2010 Sep;6(3):337-44. doi: 10.1007/s13181-010-0083-9.
After acute ingestion, acetaminophen (APAP) is generally absorbed within 4 h and the APAP concentration ([APAP]) slowly decreases with a predictable half-life. Alterations in these pharmacokinetic principles have been rarely reported. We report here three cases of an unusual double hump, or Bactrian, pattern of [APAP]. We review the literature to describe the case characteristics of these rare cases. A 38-year-old woman ingested 2 g hydrocodone/65 g acetaminophen. Her [APAP] peaked at 289 mcg/mL (8 h), decreased to 167 mcg/mL (31 h), then increased to 240 mcg/mL (39 h). She developed liver injury (peak AST 1603 IU/L; INR1.6). A 25-year-old man ingested 2 g diphenhydramine/26 g APAP. His [APAP] peaked at 211 mcg/mL (15 h), decreased to 185 mcg/mL (20 h), and increased again to 313 mcg/mL (37 h). He developed liver injury (peak AST 1153; INR 2.1). A 16-year-old boy ingested 5 g diphenhydramine and 100 g APAP. His [APAP] peaked at 470 mcg/mL (25 h), decreased to 313 mcg/mL (36 h), then increased to 354 mcg/mL (42 h). He developed liver injury (peak AST 8,686 IU/L; peak INR 5.9). We report three cases of Bactrian ("double hump") pharmacokinetics after massive APAP overdoses. Cases with double hump pharmacokinetics may be associated with large ingestions (26-100 g APAP) and are often coingested with antimuscarinics or opioids. Several factors may contribute to these altered kinetics including the insolubility of acetaminophen, APAP-induced delays in gastric emptying, opioid or antimuscarinic effects, or enterohepatic circulation. Patients with double hump APAP concentrations may be at risk for liver injury, with AST elevations and peaks occurring later than what is typical for acute APAP overdoses.
急性摄入后,对乙酰氨基酚(APAP)通常在 4 小时内被吸收,APAP 浓度 ([APAP]) 随可预测的半衰期缓慢下降。这些药代动力学原理的改变很少有报道。我们在这里报告三例不寻常的双峰或双峰驼模式的 [APAP]。我们回顾文献,描述这些罕见病例的病例特征。一名 38 岁女性摄入 2 克氢可酮/65 克对乙酰氨基酚。她的 [APAP] 峰值为 289 mcg/mL(8 小时),降至 167 mcg/mL(31 小时),然后增至 240 mcg/mL(39 小时)。她出现肝损伤(峰值 AST 1603 IU/L;INR1.6)。一名 25 岁男性摄入 2 克苯海拉明/26 克 APAP。他的 [APAP] 峰值为 211 mcg/mL(15 小时),降至 185 mcg/mL(20 小时),再次增至 313 mcg/mL(37 小时)。他出现肝损伤(峰值 AST 1153;INR 2.1)。一名 16 岁男孩摄入 5 克苯海拉明和 100 克 APAP。他的 [APAP] 峰值为 470 mcg/mL(25 小时),降至 313 mcg/mL(36 小时),然后增至 354 mcg/mL(42 小时)。他出现肝损伤(峰值 AST 8686 IU/L;峰值 INR 5.9)。我们报告了三例大剂量 APAP 过量后出现双峰(“双峰驼”)药代动力学的病例。双峰药代动力学的病例可能与大剂量摄入(26-100 克 APAP)有关,并且经常与抗毒蕈碱药物或阿片类药物同时摄入。几个因素可能导致这些改变的动力学,包括对乙酰氨基酚的不溶性、APAP 引起的胃排空延迟、阿片类药物或抗毒蕈碱药物的作用,或肠肝循环。具有双峰 APAP 浓度的患者可能有肝损伤风险,AST 升高和峰值出现时间比急性 APAP 过量典型情况晚。