The pulmonary first-pass uptake of five nondepolarizing muscle relaxants in the pig

Background: It is not known whether the lungs influence the early pharmacok inetics of muscle relaxants and, if they do, whether differences in pulmona ry uptake contribute to the differences in potency and/or onset time among muscle relaxants. Because the lungs are uniquely positioned, receive the en tire cardiac output, have a large capillary surface area, and can temporari ly store various basic drugs, the authors determined whether substantial pu lmonary first-pass uptake of muscle relaxants occurs. Methods: In 14 pigs, rocuronium, vecuronium, Org 9487, Org 7617, or d-tuboc urarine were administered simultaneously with indocyanin green within 1 s i nto the right ventricle, and then arterial blood was sampled every 1.2 s (i n the first min). The tibialis muscle response was registered mechanomyogra phically. Results: The maximum block was 93% (68-100% [median and range]). Onset time s ranged from 83 s (78-86 s) for rocuronium to 182 s (172-192 s) for d-tubo curarine. Fraction-versus-time outflow curves showed that the peak of muscl e relaxants and indocyanin green occurred almost simultaneously. Pulmonary first-pass retention was negligible. The retention of muscle relaxants at 9 5% passage of indocyanin green was -9% (-31 to 18%). The difference in the mean transit time between muscle relaxant and indocyanin green was 1.0 (0.8 to 1.4), 0.2 (-0.8 to 0.3), 0.3 (0.2 to 0.4), 0.5 (0.2 to 1.3), and -2.2 s for rocuronium, vecuronium, Org 9487, Org 7617, and d-tubocurarine, respec tively. Conclusions: There is no substantial pulmonary first-pass uptake of rocuron ium, vecuronium, Org 9487, Org 7617, or d-tubocurarine in pigs. Therefore, differences in pulmonary first-pass uptake do not contribute to the differe nces in potency and/or onset time among muscle relaxants.