Lidocaine disposition in obesity

Fourteen obese men (mean weight 124 ± 8 kg (± standard error of the mean), percent ideal body weight (IBW) 169 ± 10%), 11 obese women (96 ± 6 kg; 174 ± 11% IBW), 19 control men (69 ± 1 kg; 93 ± 2% IBW), and 12 control women (59 ± 2 kg; 102 ± 3% IBW), all of similar age and without clinical or laboratory evidence of cardiac or renal dysfunction, received a single 25-mg intravenous dose of lidocaine. Elimination half-life was markedly prolonged in obese compared with control men (2.69 ± 0.2 vs 1.62 ± 0.06 hour, p < 0.001) and in obese compared with control women (2.95 ± 0.1 vs 2.08 ± 0.06 hour, p <0.01). This was not the result of a change in clearance (men, obese vs control: 1,427 ± 117 vs 1,346 ± 86 ml/min, difference not significant, [NS]; women: 1,089 ± 83 vs 1,162 ± 84 ml/min, NS), but rather of an increased absolute volume of distribution (Vd) in obese men (325 ± 29 vs 186 ± 12 liters, p <0.001) and obese women (264 ± 20 vs 209 ± 15 liters, p <0.025). Vd corrected for total body weight was unchanged in obesity for both men (2.67 ± 0.22 vs 2.71 ± 0.18 1/kg, NS) and women (2.88 ± 0.31 vs 3.57 ± 0.25, NS), suggesting that lidocaine Vd increases in parallel with body weight in both sexes. Because lidocaine clearance is determined mainly by hepatic blood flow, these findings suggest that extremes of body weight do not change hepatic blood flow. However, lidocaine distribution is markedly increased in obese subjects of either sex, and is distributed to the same extent into excess body weight as into IBW. Lidocaine loading doses in obese persons should be calculated based on total body weight, but infusion rate should not be changed.