Johnson & Johnson Pharmaceutical Research and Development, Titusville, NJ, USA.
BMC Palliat Care. 2010 Jun 18;9:14. doi: 10.1186/1472-684X-9-14.
Little data exist on how opioid doses vary with the length of exposure among chronic opioid users.
To characterize the change in the dosage of opioids over time, a retrospective cohort study using the PharMetrics database for the years 1999 through 2008 was conducted. Individuals exposed to opioids in 2000 who had 2 opioid dispensings at least 6 months apart and were opioid naive (did not receive any opioid 6 month before their exposure in 2000) were included. The date of the first dispensing in 2000 was defined as the index date and the dispensing had to be for a strong and full agonist opioid. All opioid doses were converted to oral morphine equivalent doses. Exposure was classified as continuous or intermittent. Mean, median, interquartile range, and 95th percentile of opioid dose over 6-month periods, as well as the percentage of subjects who ever received a high or very high opioid dose, were calculated.
Among the 48,986 subjects, the mean age was 44.5 years and 54.5% were women. Intermittent exposure was observed in 99% of subjects; continuous exposure was observed in 1% of subjects. The mean duration of exposure for the subjects who were continuously exposed to opioids was 477 days. In subjects with no cancer diagnosis who were continuously exposed to opioids, the mean, 25th, 50th, and 75th percentile of dose was stable during the first 2 years of use, but the 95th percentile increased. Seven percent of them were exposed to doses of 180 mg or more of morphine at some point.
Dose escalation is uncommon in subjects with intermittent exposure to opioids. For subjects with continuous exposure to opioids who have cancer, doses rise substantially with time. For those without cancer, doses remain relatively stable for the first 2 years of use, but subsequently increase. Seven percent of subjects with no cancer diagnosis will be exposed to daily doses of 180 mg or more of morphine equivalent at some point.
慢性阿片类药物使用者的暴露时间与阿片类药物剂量之间的变化关系的数据很少。
为了描述随时间变化的阿片类药物剂量变化，我们使用 PharMetrics 数据库进行了一项回顾性队列研究，时间范围为 1999 年至 2008 年。2000 年暴露于阿片类药物且两次用药至少间隔 6 个月，并且在 2000 年暴露前 6 个月内没有接受任何阿片类药物治疗的个体被纳入研究。2000 年第一次用药的日期被定义为索引日期，并且该次用药必须是强阿片类药物和完全激动剂。所有阿片类药物剂量均转换为口服吗啡等效剂量。暴露分为连续和间断两种类型。计算了 6 个月期间阿片类药物剂量的均值、中位数、四分位间距和 95%分位数，以及曾经接受高剂量或非常高剂量阿片类药物的受试者比例。
在 48986 名受试者中，平均年龄为 44.5 岁，54.5%为女性。99%的受试者间断暴露，1%的受试者连续暴露。连续暴露于阿片类药物的受试者的平均暴露时间为 477 天。在未诊断患有癌症且连续暴露于阿片类药物的受试者中，在使用的前 2 年内，剂量的均值、25%分位数、50%分位数和 75%分位数保持稳定，但 95%分位数增加。其中 7%的人在某个时间点暴露于 180mg 或更高剂量的吗啡。
间断暴露于阿片类药物的受试者中剂量逐渐增加的情况并不常见。对于患有癌症且连续暴露于阿片类药物的受试者，剂量随时间显著增加。对于未患有癌症的受试者，在使用的前 2 年内剂量相对稳定，但随后增加。7%的未诊断患有癌症的受试者在某个时间点将暴露于每日 180mg 或更高剂量的吗啡等效药物。
