Ethnicity influences morphine pharmacokinetics and pharmacodynamics

Abstract

Objective: Our objective was to evaluate ethnic differences in response to morphine and to determine whether any detectable differences were pharmacokinetically based.

Methods: This cohort study was carried out in a teaching hospital. Sixty-six young, healthy male subjects from 3 ethnic groups (Caucasians, native Indians, and Latinos; n = 22 in each group) consented to participate. All subjects received an intravenous morphine bolus of 0.08 mg/kg followed by 0.002 mg/kg. min infused for 30 minutes. Respiratory response was evaluated with the carbon dioxide rebreathing method before and at 25, 95, 180, and 360 minutes after morphine administration. Vital signs and opioid side effects were recorded, and serial blood samples were analyzed for morphine, morphine-3-glucuronide, and morphine-6-glucuronide (M6G).

Results: All 3 groups had suppression of the ventilatory response to hypercapnia, but the degree of blunting of the ventilatory response differed among groups. Compared with Caucasians, native Indians had an additional 18% reduction in ventilatory response after morphine administration (95% confidence interval, -35% to -2%). The incidence of side effects was similar in all groups (P =.18). Caucasians had higher plasma levels of M6G than did native Indians or Latinos. M6G areas under 6-hour concentration-versus-time curve were as follows: Caucasians, 12,065 +/- 4354; native Indians, 8464 +/- 4809; and Latinos, 9156 +/- 3764 ng. min/mL (P =.03).

Conclusions: Ethnicity influences the response to morphine. Native Indians are more susceptible to morphine depression of the ventilatory response than Caucasians, despite the higher serum M6G levels in Caucasians.